Immunization of immunocompromised persons: Canadian Immunization Guide

For health professionals

Notice

This chapter has not yet been updated with the following statements from the National Advisory Committee on Immunization (NACI):

March 11, 2024: Recommendations for public health programs on the use of pneumococcal vaccines in children, including the use of 15-valent and 20-valent conjugate vaccines
March 21, 2023: Interim guidance on the use of pneumococcal 15-valent conjugate vaccine (PNEU-C-15) in pediatric populations
February 24, 2023: Public health level recommendations on the use of pneumococcal vaccines in adults, including the use of 15-valent and 20-valent conjugate vaccines.

This CIG chapter has not been completely updated to contain all pertinent information regarding COVID-19 vaccines. For this information, refer to the COVID-19 vaccine chapter.

Last partial content update: March 2023

This chapter was updated to incorporate guidance from the National Advisory Committee on Immunization (NACI) statement: Recommended use of palivizumab to reduce complications of respiratory syncytial virus infection in infants.

This information is captured in the table of updates.

Last complete chapter revision: May 2018

Introduction and general principles

Individuals may be immunocompromised as a result of a congenital condition, an illness or medications that suppress immune function. In general, immunocompromised persons are more susceptible to vaccine-preventable infections and may have severe infections. The safety and effectiveness of vaccines in immunocompromised persons are determined by the type of immunodeficiency and degree of immunosuppression. Each immunocompromised person is different and presents unique considerations regarding immunization. The relative degree of immunodeficiency is variable depending on the underlying condition, the progression of disease and use of immunosuppressive agents. Immunodeficiency can also vary over time in many people and the decision to recommend for or against a particular vaccine will depend upon a case-by-case analysis of the risks and benefits. There is potential for serious illness and death if immunocompromised people are under-immunized and every effort should be made to ensure adequate protection through immunization; however, inappropriate use of live vaccines can cause serious adverse events in some immunocompromised people as a result of uncontrolled replication of the vaccine virus or bacterium.

Primary care providers and specialists caring for immunocompromised patients share responsibility for ensuring appropriate vaccination of immunocompromised patients and their households. When in doubt, primary care providers should consult a specialist with experience in managing patients with the specific immunocompromising condition of concern.

The following recommendations reflect general best practices and are subject to individual considerations and new evidence as it arises.

Non-live vaccines

Non-live vaccines, including inactivated and recombinant, may generally be administered to immunocompromised people if indicated because the antigens in the vaccine cannot replicate and there is no increase in the risk of vaccine-associated adverse events; however, the magnitude and duration of vaccine-induced immunity are often reduced. For complex cases, referral to a physician with expertise in immunization and/or immunodeficiency is advised.

Live attenuated vaccines

In general, people who are severely immunocompromised or in whom immune status is uncertain should not receive live vaccines because of the risk of disease caused by the vaccine strains. In less severely immunocompromised people, the benefits of vaccination with routinely recommended live vaccines may outweigh risks. Before giving an immunocompromised person a live vaccine, a physician with expertise in immunodeficiency should be consulted.

Immunoglobulins

For temporary passive protection against some infections, immunoglobulin therapy (nonspecific or pathogen specific) may be indicated for pre or post exposure. The monoclonal antibody preparation, Palivizumab (Synagis™) is an antibody directed specifically against respiratory syncytial virus (RSV) that may be considered to reduce complications of RSV infection in children less than 24 months of age who are severely immunocompromised.

Serologic testing and re-immunization

Immune response to vaccines may be inadequate in immunocompromised people and vaccinees may remain susceptible despite vaccination. If serologic testing is available and there is a clear antibody correlate of protection, measurement of post-immunization antibody titres to determine immune response and guide re-vaccination and post-exposure management should be considered. For infants less than 18 months of age, a positive serologic test may detect maternal antibody and not reflect an active immune response in the infant. Seroconversion or an increase in titre, or a repeat test after 18 months of age showing persistent antibody, indicate an active response. Results of serologic testing may also be confounded by passive antibody in those receiving immunoglobulin therapy.

Please note that the information in the text and tables is complementary and both should be used. Refer to vaccine-specific chapters in Part 4 for additional information, especially concerning vaccine doses, schedules and boosters.

General principles

Several general principles apply to the immunization of immunocompromised individuals:

Maximize benefit while minimizing harm.
Susceptibility to infection and ability to respond to a vaccine vary according to degree of immune suppression.
Immunize at the time when maximum immune response can be anticipated.
- Immunize prior to any planned immunosuppression, if possible.
- Delay immunization if the immunodeficiency is transient (if this can be done safely because exposure is unlikely).
- Stop or reduce immunosuppression to permit better vaccine response, if appropriate.
Consider the immunization environment broadly.
- Vaccinate family members and other close contacts when appropriate.
- Strongly encourage up-to-date vaccinations, including annual influenza vaccination, for all healthcare workers providing care to immunocompromised people.
Avoid live vaccines unless:
- immunosuppression is mild and data are available to support their use.
- the risk of natural infection is greater than the risk of immunization.
Monitor serologic response, if appropriate test and correlate of protection is available, and boost if antibody level is inadequate.
- The magnitude and duration of vaccine-induced immunity are often reduced in immunocompromised individuals.

Family or medical history

Primary or secondary immunodeficiencies may be undiagnosed in young children presenting for routine immunizations, which include live vaccines. This is particularly important to consider in infants receiving live vaccines before 12 months of age.

A significant primary immunodeficiency in which live vaccines would be contraindicated usually declares itself in the first few months of life. The only live vaccine routinely given to children less than 12 months of age is rotavirus, which can be given as early as 6 weeks of age. Chronic rotavirus infection from the vaccine strain has occurred in infants with unrecognized severe combined immunodeficiency. BCG vaccine is given at birth in some populations. Measles vaccine may be given at 6-12 months of age in an outbreak, after exposure or for children travelling outside of Canada or to locations experiencing outbreaks.

Clues pointing to the presence of significant immunodeficiency may be found in the medical or family history. Infants with a history of failure to thrive, recurrent or prolonged oral candidiasis despite treatment, or recurrent serious infections such as pneumonia or sepsis may have an immunodeficiency. A family history of primary immunodeficiency may be known or may be suspected on the basis of a family history of early infant deaths. However, the family history can be negative. Routine newborn screening for severe combined immunodeficiency is now performed in some regions of Canada. Maternal human immunodeficiency virus (HIV) infection puts the infant at risk of immunodeficiency in the first year of life if HIV has been transmitted to the infant. Routine prenatal blood work in Canada includes HIV testing. If an infant shows clinical clues suggesting immunodeficiency, the mother's prenatal HIV screening result should be obtained. If a mother was not screened in pregnancy, the possibility of perinatal HIV infection from undiagnosed maternal infection should be considered.

Primary immunodeficiency

There are currently more than 300 distinct genetic defects of immunity. These are grouped under general headings below.

Refer to Immunization of Persons with Chronic Diseases in Part 3 for information regarding immunization of asplenic or hyposplenic people.

Predominantly antibody (B cell) deficiencies

B cell defects (defects of humoral immunity) include X-linked agammaglobulinemia (XLA), common variable immunodeficiency (CVID), selective immunoglobulin A (IgA) deficiency, specific polysaccharide antibody deficiency (SPAD), and immunoglobulin G (IgG) subclass deficiency.

Individuals with defects in antibody production are highly susceptible to encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.

Most patients with severe defects of antibody production, such as XLA or CVID are not able to mount a significant humoral response. While administration of non-live vaccines is not harmful, it may be futile. As a general rule, people with severe antibody defects can be protected from many of the vaccine preventable infections with the use of replacement immunoglobulin (Ig) therapy or pathogen-specific Ig preparations; however, the level of antibody to specific pathogens in these products may be variable.
For those with less severe antibody deficiency and expected ability to mount some antibody response, especially selective IgA deficiency or IgG subclass deficiency, vaccination is recommended to increase the level of protection. Receipt of replacement Ig is not a contraindication for use of non-live vaccines; however, Ig can interfere with the immune response to some live attenuated viral vaccines such as measles and varicella vaccine.
Repeat doses of Ig should not be given to individuals with known selective IgA deficiency unless the benefit outweighs the risk, because of the very rare risk of an anaphylactic reaction to traces of IgA in the product. If indicated, an Ig product with the least amount of IgA should be used and given with caution under close observation.

Non-live vaccines

In general, non-live vaccines should be administered according to routine immunization schedules to people with less severe primary B cell defects who have some capacity for B or T cell responses. Hepatitis B vaccine should be given at double the routine dose and using a 3- or 4-dose schedule. Human papillomavirus (HPV) vaccine should be given following routine age indications but using a 3-dose schedule regardless of age.

In addition to routine vaccines, individuals with primary B cell defects should receive pneumococcal conjugate vaccine regardless of age, pneumococcal polysaccharide vaccine if 2 years of age or older, and one dose of Haemophilus influenzae type b (Hib) vaccine after age 5 years regardless of prior Hib vaccination history. Quadrivalent conjugate meningococcal vaccine is recommended and serogroup B meningococcal vaccine should be offered if 2 months of age or older. Booster doses of quadrivalent conjugate meningococcal vaccine are recommended every 3 to 5 years depending on age of initial vaccination. For serogroup B meningococcal vaccines, the timing of booster doses is yet to be determined.

Live attenuated vaccines

Patients with severe B cell defects (XLA, CVID), and others receiving regular immunoglobulin replacement therapy, should not receive measles-mumps-rubella (MMR), measles-mumps-rubella-varicella (MMRV) or varicella vaccines as Ig will interfere with the efficacy of these vaccines.

Individuals with partial B cell defects and known intact T cell immunity and some ability to produce antibody who are not receiving Ig should receive MMR and univalent varicella vaccines as appropriate for age. MMRV has not been evaluated in immunodeficiency. All other live vaccines such as rotavirus, live attenuated influenza, Bacille Calmette-Guérin (BCG), oral polio, smallpox, oral typhoid and yellow fever vaccines are contraindicated. If travel to an area where yellow fever is being transmitted cannot be avoided, consideration of vaccination in consultation with a specialist is advised.

People with selective IgA deficiency who have no concomitant defects in T cell function can receive most live vaccines. Live mucosal vaccines (rotavirus, live attenuated influenza vaccine (LAIV), oral typhoid) are likely safe and may be used although there may be lack of mucosal response. Some experts prefer to use non-live vaccines if available (e.g., inactivated influenza vaccine, parenteral inactivated typhoid vaccine). However, given that there are limited data on the use of live mucosal vaccines, consultation with an immunologist is advised and immunization with these vaccines should be individually assessed.

The diagnosis of IgG subclass deficiency should be based on documented failure to produce adequate amounts of specific antibody and not on quantitative Ig levels. Individuals with documented IgG subclass deficiency with intact T cell function who are not receiving regular Ig replacement therapy can receive routine live vaccines although response may be suboptimal. All live vaccines may be given to individuals with isolated SPAD.

Refer to Blood Products, Human Immunoglobulin and Timing of Immunization in Part 1 for the recommended intervals between Ig and subsequent immunization.

Refer to Table 1 and Table 2 and vaccine-specific chapters in Part 4 for additional information.

Combined T and B cell immunodeficiencies (with or without associated /syndromic features) and Immune dysregulation

Individuals with T cell or combined deficiency are particularly susceptible to infections with virtually all viruses and many bacteria. T cell defects may be severe (e.g., severe combined immunodeficiency, complete DiGeorge syndrome) or partial (e.g., DiGeorge syndrome, Wiskott-Aldrich syndrome, ataxia telangiectasia, hyper IgM syndrome, hyper IgE syndrome, X-linked lymphoproliferative disease, familial predisposition to hemophagocytic lymphohistiocytosis). Those with severe defects will not respond to any vaccines. Those with partial defects may have some response.

Non-live vaccines

For those with severe combined immunodeficiency, administration of non-live vaccines is not harmful, but will not provide protection.

Non-live vaccines should be given to those with partial immunodeficiency although response may be suboptimal. Hepatitis B vaccine should be given at double the routine dose and using a routine 3- or 4-dose schedule. HPV vaccine should be given following routine age indications but using a 3-dose schedule regardless of age.

In addition to routine vaccines, individuals with partial T cell or combined defects should receive pneumococcal conjugate vaccine regardless of age, pneumococcal polysaccharide vaccine if 2 years of age or older, and one dose of Hib vaccine after age 5 years regardless of prior Hib vaccination history. Quadrivalent conjugate meningococcal vaccine is recommended and serogroup B meningococcal vaccine should be offered if 2 months of age or older. Booster doses of quadrivalent conjugate meningococcal vaccine are recommended every 3 to 5 years depending on age of initial vaccination. For serogroup B meningococcal vaccines, the timing of booster doses is yet to be determined.

Non-live influenza vaccine should be given annually, as Ig may not protect. However, humoral response may be reduced.

Live attenuated vaccines

All live attenuated vaccines are contraindicated for individuals with severe T cell defects. Exposure to natural infection or inadvertent live attenuated vaccine administration can usually be managed with rapid administration of Ig or pathogen-specific Ig with or without appropriate antiviral treatment. Live vaccines are also generally contraindicated for those with Wiskott-Aldrich syndrome, ataxia telangiectasia, X-linked lymphoproliferative disease, or familial predisposition to hemophagocytic lymphohistiocytosis.

Live attenuated vaccines may be considered for those with partial T cell defects after assessment of immune competence. Those with partial DiGeorge syndrome, or other combined defects, and a total CD4 lymphocyte count of > 500 x 10⁶/L and normal mitogen response should receive MMR and univalent varicella vaccines as MMRV has not been evaluated in this population. MMRV and other live vaccines are contraindicated.

Refer to Blood Products, Human Immunoglobulin and Timing of Immunization in Part 1 for the recommended intervals between Ig and subsequent immunization.

Refer to Table 1, Table 2 and vaccine-specific chapters in Part 4 for additional information.

Phagocytic and neutrophil disorders

People with phagocytic and neutrophil disorders (e.g., congenital neutropenia, cyclic neutropenia, leukocyte adhesion and migration defects, chronic granulomatous disease (CGD), myeloperoxidase deficiency and Chediak-Higashi syndrome) are at increased risk for bacterial infections.

Non-live vaccines

All routine non-live vaccines and others required because of travel or exposure should be given. Pneumococcal conjugate vaccine (regardless of age) and pneumococcal polysaccharide vaccine if 2 years of age or older are indicated for all conditions other than CGD. CGD does not increase the risk of invasive pneumococcal disease, so conjugate vaccine should be used according to routine schedules and polysaccharide vaccine is not indicated. Non-live influenza vaccine should be given annually. Influenza vaccine is especially important in patients with CGD due to increased morbidity and mortality with staphylococcal lung infections that are associated with influenza.

Live attenuated vaccines

Live bacterial vaccines (BCG, oral typhoid) are contraindicated in all phagocytic or neutrophil defects. Live attenuated viral vaccines (rotavirus, MMR, varicella, MMRV) should be given according to routine schedules to persons with neutropenia or CGD, and live attenuated influenza vaccine (LAIV) or yellow fever vaccine may be given if indicated. All live attenuated viral vaccines are contraindicated with leukocyte adhesion defect (LAD), Chediak-Higashi syndrome and other defects in cytotoxic granule release, and in any other undefined phagocytic cell defect.

Refer to Table 1, Table 2 and vaccine-specific chapters in Part 4 for additional information.

Complement deficiency

Individuals with complement, properdin, factor D or B or mannan-binding lectin deficiency are particularly susceptible to infections with N. meningitidis but also susceptible to other encapsulated bacteria such as S. pneumoniae and Haemophilus influenzae. In general, response to vaccines is expected to be normal and there are no contraindications.

Non-live vaccines

Non-live vaccines should be administered according to routine immunization schedules.

In addition to routine vaccines, quadrivalent conjugate meningococcal vaccine is recommended and serogroup B meningococcal vaccine should be offered if 2 months of age or older. Booster doses of quadrivalent conjugate meningococcal vaccine are recommended every 3 to 5 years depending on age of initial vaccination. For serogroup B meningococcal vaccines, the timing of booster doses is yet to be determined.

Pneumococcal conjugate vaccine should be given regardless of age, pneumococcal polysaccharide vaccine if 2 years of age or older, and one dose of Hib vaccine after age 5 years regardless of prior Hib vaccination history. Influenza vaccine (non-live or live attenuated, as appropriate for age) should be given annually.

Live attenuated vaccines

Individuals with complement deficiency should receive all routine live attenuated vaccines and any other live vaccines that are indicated (e.g., for travel or after exposure).

Refer to Table 1, Table 2 and vaccine-specific chapters in Part 4 for additional information.

Defects of innate immunity

Innate immune defects of cytokine generation or cellular activation, such as defects of the interferon-gamma/interleukin-12 axis, increase susceptibility to mycobacterial disease. Toll-like receptor signaling pathway deficiencies (i.e. IRAK4 and MyD88 deficiency) increase susceptibility to pneumococcal and other pyogenic bacterial infections. Some innate defects may result in increased susceptibility to viral infections.

Non-live vaccines

All routine non-live vaccines should be given. Persons with IRAK4 and MyD88 deficiency or other defects causing increased risk for pyogenic bacterial infections should receive conjugate pneumococcal vaccine regardless of age and polysaccharide pneumococcal vaccine at age ≥ 2 years. Other non-live vaccines should be used as indicated for travel or exposure.

Live attenuated vaccines

A specialist should be consulted before giving live vaccines to persons with innate immune defects of cytokine generation or response or cellular activation defects. Persons with interferon gamma/interleukin-12 axis defects have a greater susceptibility to intracellular bacteria (i.e. salmonella or mycobacteria). For those patients, live bacterial vaccines (BCG, oral typhoid) are contraindicated. Live viral vaccines are contraindicated in patients with defects in alpha/beta or gamma interferon production. All live vaccines are contraindicated in nuclear factor kappa B pathway defects.

Refer to Table 1 and Table 2 for recommendations for vaccination of persons with primary immunodeficiencies and to vaccine-specific chapters in Part 4 for additional information.

Table 1: Vaccination of persons with primary immunodeficiencies - Non-live vaccines
Non-live vaccines	Primary Immunodeficiency					Comments
Non-live vaccines	B cell deficiency^{Footnote 1}	Combined T, B cell deficiency^{Footnote 1}	Phagocytic & neutrophil disorders	Complement deficiency	Innate immune defects	Comments
Cholera and travellers' diarrhea (inactivated)	Use if indicated	Use if indicated	Use if indicated	Use if indicated	Use if indicated
Diphtheria^{Footnote 2}	Routine use^{Footnote 3}	Routine use^{Footnote 3}	Routine use^{Footnote 3}	Routine use^{Footnote 3}	Routine use^{Footnote 3}
Haemophilus influenzae type b (Hib)^{Footnote 4}	Children less than 5 years of age: routine use	Children less than 5 years of age: routine use	Children less than 5 years of age: routine use	Children less than 5 years of age: routine use	Children less than 5 years of age: routine use
Haemophilus influenzae type b (Hib)^{Footnote 4}	Individuals 5 years of age and older: 1 dose recommended^{Footnote 5}	Individuals 5 years of age and older: 1 dose recommended^{Footnote 5}		Individuals 5 years of age and older: 1 dose recommended^{Footnote 5}
Hepatitis A	Use if indicated^{Footnote 6}	Use if indicated^{Footnote 6}	Use if indicated	Use if indicated	Use if indicated^{Footnote 6}
Hepatitis B	Recommended^{Footnote 7}^{Footnote 8}^{Footnote 9}	Recommended^{Footnote 7}^{Footnote 8}^{Footnote 9}	Routine Use	Routine Use	Routine Use
Herpes zoster (non-live recombinant)	Consider if indicated by age^{Footnote 10}	Consider if indicated by age^{Footnote 10}	Consider if indicated by age^{Footnote 10}	Consider if indicated by age^{Footnote 10}	Consider if indicated by age^{Footnote 10}
HPV	Routine use^{Footnote 3}	Routine use^{Footnote 3}	Routine use^{Footnote 3}	Routine use^{Footnote 3}	Routine use^{Footnote 3}	3-dose schedule recommended
Influenza (inactivated or recombinant)	Recommended annually	Recommended annually	Recommended annually	Recommended annually	Recommended annually
Japanese encephalitis	Use if indicated	Use if indicated	Use if indicated	Use if indicated	Use if indicated
Meningococcal, quadrivalent conjugate	Recommended	Recommended	Routine use	Recommended	Routine use	If indicated, administer from 2 months of age. Booster doses required every 3-5 years depending on age of initial vaccination^{Footnote 11}.
Meningococcal, serogroup B	Should be offered	Should be offered	Use if indicated	Should be offered	Use if indicated	If indicated, administer from 2 months of age^{Footnote 12}. The timing of booster doses has not yet been determined.
Pertussis^{Footnote 2}	Routine use^{Footnote 3}	Routine use^{Footnote 3}	Routine use^{Footnote 3}	Routine use^{Footnote 3}	Routine use^{Footnote 3}
Pneumococcal conjugate 13-valent (Pneu-C-13)	Recommended regardless of age	Recommended regardless of age	Recommended regardless of age^{Footnote 13}	Recommended regardless of age	Recommended regardless of age	Should be followed, at age at least 2 years and at least 2 months after last dose with pneumococcal polysaccharide vaccine
Pneumococcal polysaccharide (Pneu-P-23)	Recommended if 2 years of age or older	Recommended if 2 years of age or older	Recommended if 2 years of age or older^{Footnote 13}	Recommended if 2 years of age or older	Use if indicated^{Footnote 14}	One re-immunization recommended 5 years after first dose
Polio^{Footnote 2} (inactivated)	Routine use^{Footnote 3}	Routine use^{Footnote 3}	Routine use^{Footnote 3}	Routine use^{Footnote 3}	Routine use^{Footnote 3}
Rabies	Use if indicated	Use if indicated	Use if indicated	Use if indicated	Use if indicated	Do not use intradermally Use 5 dose schedule for post exposure prophylaxis Post-immunization serology recommended
Tetanus^{Footnote 2}	Routine use^{Footnote 3}	Routine use^{Footnote 3}	Routine use^{Footnote 3}	Routine use^{Footnote 3}	Routine use^{Footnote 3}
Typhoid (inactivated)	Use if indicated	Use if indicated	Use if indicated	Use if indicated	Use if indicated
Abbreviations: anti-HBs antibody to hepatitis B surface antigen Ig immunoglobulin Footnote 1 Most patients with severe B cell deficiency (e.g., X-linked agammaglobulinemia, common variable immunodeficiency) and patients with severe T cell defects (e.g., severe combined immunodeficiency, complete DiGeorge syndrome) are unable to respond to any vaccine. Non-live vaccines are safe but not effective. They should be given only if some antibody production is expected. Those with less severe defects should receive non-live vaccines as indicated here. Return to footnote 1 referrer Footnote 2 Given as combined vaccine (diphtheria, tetanus, pertussis; ± polio, Hib depending on age and previous vaccine history). Return to footnote 2 referrer Footnote 3 Routine use: Follow routine immunization schedules with age-appropriate booster doses. Return to footnote 3 referrer Footnote 4 May be given as combined vaccine. Return to footnote 4 referrer Footnote 5 Regardless of prior history of Hib vaccination and at least 1 year after any previous dose. Return to footnote 5 referrer Footnote 6 Pre-exposure prophylaxis for travel: consider Ig with hepatitis A vaccine unless receiving routine IG replacement therapy. Post-exposure prophylaxis: Ig recommended in addition to vaccine unless receiving routine IG replacement therapy. Return to footnote 6 referrer Footnote 7 Double the routine dose and use 3 or 4 dose schedule. Return to first footnote 7 referrer Footnote 8 Initially annual monitoring of antibody levels may be considered. Optimal timing and frequency should be based on the severity of the immunocompromised state and the ongoing risk of acquisition of HB infection. Return to first footnote 8 referrer Footnote 9 Post-immunization monitoring of anti-HBs titres recommended with booster dose if titre less than 10 IU/L. Return to footnote 9 referrer Footnote 10 Non-live recombinant zoster vaccine may be considered in immunocompromised adults ≥ 50 years of age on a case by case basis. Data on the use in immunocompromised individuals is limited, but based on the burden of zoster illness in this population and the general safety of inactivated vaccines, the benefits of vaccination are expected to outweigh the risks. Return to footnote 10 referrer Footnote 11 Refer to Meningococcal Vaccine, Booster doses and re-immunization in Part 4 (https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-13-meningococcal-vaccine.html#booster) for additional information for re-vaccination recommendations and intervals. Return to footnote 11 referrer Footnote 12 4CMenB vaccine is indicated for immunization of high risk individuals greater than or equal to two months of age; MenB-fHBP vaccine may be considered as an option for use in high-risk individuals 10 years of age and older. Return to footnote 12 referrer Footnote 13 For CGD, give pneumococcal conjugate vaccine according to the routine schedule; pneumococcal polysaccharide vaccine is not indicated. Return to footnote 13 referrer Footnote 14 Persons with IRAK4 and MyD88 deficiency or other innate defects causing increased risk for pyogenic bacterial infections should receive polysaccharide pneumococcal vaccine at age ≥ 2 years. Return to footnote 14 referrer

Table 2: Vaccination of persons with primary immunodeficiencies - Live attenuated vaccines
Live attenuated vaccines	Primary Immunodeficiency
Live attenuated vaccines	Minor B cell deficiency^{Footnote 1} (Partial B cell defects, IgA deficiency, IgG subclass deficiency, SPAD)	Partial T cell, combined T, B deficiency^{Footnote 2}	Phagocytic & neutrophil disorders (see exceptions)^{Footnote 3}	Complement deficiency	Innate immune defects^{Footnote 4}
BCG	Contraindicated for minor B cell deficiencies except for isolated IgA deficiency, IgG subclass deficiency, SPAD: use if indicated	Contraindicated	Contraindicated	Use if indicated	Contraindicated
Influenza (live)	Contraindicated for minor B cell deficiencies except for isolated IgA deficiency, IgG subclass deficiency, SPAD: Consider use^{Footnote 5}	Contraindicated - use non-live	Use if indicated	Use if indicated	Consult specialist
MMR	Routine use^{Footnote 6}^{Footnote 7}^{Footnote 8}	Use if T cell function meets criteria (see text)^{Footnote 6}	Routine use	Routine use	Consult specialist
MMRV	Contraindicated for minor B cell deficiencies except for isolated IgA deficiency, IgG subclass deficiency, SPAD: Consider use	Contraindicated	Routine use	Routine use	Consult specialist
Rotavirus	Contraindicated for minor B cell deficiencies except for isolated IgA deficiency, IgG subclass deficiency, SPAD: Consider use	Contraindicated	Routine use	Routine use	Consult specialist
Smallpox	Contraindicated for minor B cell deficiencies except for isolated IgA deficiency, IgG subclass deficiency, SPAD: Use if indicated	Contraindicated	Use if indicated	Use if indicated	Consult specialist
Typhoid (live)	Contraindicated for minor B cell deficiencies except for isolated IgA deficiency, IgG subclass deficiency, SPAD: Consider use^{Footnote 5}	Contraindicated; if indicated, use non-live	Contraindicated; if indicated, use non-live	Use if indicated	Contraindicated; if indicated use non-live
Varicella (univalent)	Routine use^{Footnote 6}^{Footnote 7}^{Footnote 8}	Use if T cell function meets criteria (see text)^{Footnote 6}	Routine use	Routine use	Consult specialist
Yellow fever	Contraindicated for minor B cell deficiencies except for isolated IgA deficiency, IgG subclass deficiency, SPAD: Use if indicated^{Footnote 9}	Contraindicated	Use if indicated	Use if indicated	Consult specialist
Abbreviation: Ig immunoglobulin Footnote 1 Major B cell deficiency: X-linked agammaglobulinemia, common variable immunodeficiency and other major antibody defects: all live vaccines contraindicated. Those with partial B cell defects and known intact T cell function who are not receiving regular Ig therapy may receive MMR and varicella vaccines. Other live vaccines are contraindicated. Return to footnote 1 referrer Footnote 2 Severe combined immunodeficiency, complete DiGeorge syndrome and others with severe T cell deficiency: all live vaccines contraindicated. Those with partial defects (see text) may receive MMR and varicella vaccine. Return to footnote 2 referrer Footnote 3 All live vaccines contraindicated with leukocyte adhesion defect, Chediak-Higashi syndrome and other defects in cytotoxic granule release, and any other undefined phagocyte defect. Return to footnote 3 referrer Footnote 4 A specialist should be consulted before giving live vaccines to persons with defects of cytokine generation / response or cellular activation defects. Live bacterial vaccines are contraindicated in defects of interferon gamma/interleukin-12 pathways. Live viral vaccines are contraindicated in patients with defects of alpha or gamma interferon production. All live vaccines are contraindicated in nuclear factor kappa B pathway defects. Return to footnote 4 referrer Footnote 5 Consult with immunologist in cases of IgA deficiency; some experts may prefer inactivated vaccine for persons with IgA deficiency. Return to footnote 5 referrer Footnote 6 B or T cell or combined deficiency: consider post-immunization serology and re-immunize if protective titres not achieved. Return to footnote 6 referrer Footnote 7 Routine use: follow routine immunization schedules with age-appropriate booster doses. Return to footnote 7 referrer Footnote 8 Regular immunoglobulin replacement therapy will affect the efficacy of the vaccine. Refer to Blood products, human immunoglobulin and timing of immunization in Part 1 (https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-1-key-immunization-information/page-11-blood-products-human-immune-globulin-timing-immunization.html) for the recommended intervals between Ig and subsequent immunization. Return to footnote 8 referrer Footnote 9 If travel to an area where yellow fever is being transmitted cannot be avoided, consider use of the vaccine in consultation with a specialist. Return to footnote 9 referrer

Acquired (secondary) immunodeficiency

Acquired immunodeficiency states result from medical conditions that directly or indirectly cause immunosuppression (e.g., malignant hematologic disorders or solid tumours, hematopoietic stem cell transplantation, HIV-infection). Acquired immunodeficiency may also occur due to immunosuppressive therapies (e.g., long-term steroid treatment, cancer chemotherapy, other cytotoxic therapy, biological response modifiers, calcineurin inhibitors, radiation therapy) used to treat these conditions as well as to treat solid organ transplant recipients and a range of chronic inflammatory conditions (e.g., inflammatory bowel disease, arthritis, psoriasis, systemic lupus erythematosus).

Refer to Immunization of persons with chronic diseases in Part 3 for information regarding immunization of asplenic or hyposplenic people, as well as other chronic diseases.

Acquired complement deficiency

People who are receiving the terminal complement inhibitor eculizumab (SOLIRIS^®, Alexion Pharma GmbH) or ravulizumab (ULTOMIRIS^®, Alexion Pharma GmbH) for paroxysmal nocturnal hemoglobinuria, atypical hemolytic-uremic syndrome or other conditions are at high risk of invasive meningococcal infections. In addition to all age-appropriate routine vaccines, quadrivalent conjugate meningococcal vaccine is recommended and serogroup B meningococcal vaccine should be offered. They must be vaccinated at least 2 weeks prior to receiving the first dose of eculizumab or ravulizumab, if possible. Booster doses of quadrivalent conjugate meningococcal vaccine are recommended every 3 to 5 years, depending on age of initial vaccination, if they continue to use the drug. For serogroup B meningococcal vaccines, the timing of booster doses is yet to be determined.

Hemolysis can be precipitated by the combination of meningococcal B vaccines and eculizumab or ravulizumab if the underlying hemolytic condition is not yet under control. For patients already receiving eculizumab or ravulizumab, meningococcal B vaccine should be given after the underlying hemolytic condition is under control and less than one week after a dose of eculizumab or ravulizumab.

For more information, refer to the Health Canada, Health professional risk communication: SOLIRIS (eculizumab) - Increased Risk of Hemolysis or Low Hemoglobin with Serogroup B Meningococcal Vaccination and the SOLIRIS^® Product Monograph available through Health Canada’s Drug Product Database.

Refer to Meningococcal Vaccine, Booster doses and re-immunization in Part 4 for additional information for re-vaccination recommendations and intervals.

Malignant hematologic disorders

(e.g., leukemia, lymphomas, blood dyscrasias or other malignant neoplasms affecting the bone marrow or lymphatic systems)

Non-live vaccines

In general, non-live vaccines should be administered to people with malignant hematologic disorders according to routine immunization schedules, although response may be sub-optimal. Immunization should be given at least 2 weeks prior to the start of immunosuppressive therapy or when immunosuppressive therapy is at the lowest level unless the risk of imminent exposure to the pathogen is high. Hepatitis B vaccine should be given at double the routine dose and using a 3 or 4 dose schedule. HPV vaccine should be given following routine age indications but using a 3 dose schedule regardless of age. Doses of any vaccine received while on immunosuppressive therapy should be repeated once no longer immune suppressed, unless an adequate antibody response can be demonstrated.

Individuals with malignant hematologic neoplasms should also receive conjugate pneumococcal vaccine (regardless of age), pneumococcal polysaccharide vaccine if age 2 years or more, and one dose of Hib vaccine after age 5 years regardless of prior Hib vaccination history, because of increased susceptibility to these infections. For infants 6 months of age or older, annual immunization with inactivated influenza vaccine is also recommended.

Live attenuated vaccines

Live attenuated vaccines are contraindicated in individuals with severe immunodeficiency due to blood dyscrasias, lymphomas, leukemias of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems and in people undergoing immunosuppressive chemotherapy or radiotherapy treatment for these conditions.

In general, if the cancer is in remission and chemotherapy and/or radiotherapy have been completed for at least 3 months, and T cell function is normal, the person is no longer considered immunocompromised and live vaccines may be given. Live vaccines should be deferred for at least 6 months after therapy with anti B-cell antibody.

Non-hematologic malignant solid tumours

Non-live vaccines

Non-live vaccines should be administered to people with malignant solid tumours according to routine immunization schedules. Immunization should be given at least 2 weeks prior to the start of immunosuppressive therapy or when immunosuppressive therapy is at the lowest level unless the risk of imminent exposure to the pathogen is high. Hepatitis B vaccine should be given at double the routine dose and using a 3- or 4-dose schedule. HPV vaccine should be given following routine age indications but using a 3-dose schedule regardless of age. Doses of any vaccine received while on immunosuppressive therapy should be repeated once no longer immune suppressed unless an adequate antibody response can be demonstrated.

In addition, pneumococcal conjugate vaccine (regardless of age) and polysaccharide vaccine (if age 2 years or more) should be given because of increased susceptibility to invasive pneumococcal disease. For infants 6 months of age or older, annual immunization with inactivated influenza vaccine is also recommended.

Live attenuated vaccines

Live vaccines are contraindicated in people undergoing immunosuppressive treatment for any malignant solid tumour. In general, if chemotherapy has been completed for at least 3 months and the cancer is in remission, the person is no longer considered immunocompromised.

Hematopoietic stem cell transplantation (HSCT): autologous or allogeneic

HSCT is the transplantation of hematopoietic stem cells following bone marrow ablation or non-ablative conditioning (chemotherapy and/or radiotherapy to deplete the hematopoietic system prior to transplant). HSCT recipients receive either their own cells (autologous HSCT) or cells from a donor (allogeneic HSCT). Stem cells are sourced from bone marrow, peripheral blood, or umbilical cord blood.

Virtually all HSCT recipients experience a prolonged period of immune suppression following transplantation. Antibody titres to vaccine-preventable diseases decrease after allogeneic or autologous HSCT. Duration of immune suppression varies, depending on type of transplant (allogeneic or autologous), stem cell source, stem cell manipulation and post-transplant complications. Allogeneic HSCT recipients experience profound immune suppression in the post-transplant period, with recovery of the immune system approximately 1-2 years after HSCT. However, this recovery is delayed in the presence of immunosuppressive medication and chronic graft-versus-host disease (cGVHD). Recovery usually occurs earlier after autologous HSCT but still requires several months.

In general, T cells capable of responding to new antigens are generated at 6 to 12 months after transplant, earlier in young children and later in adults. Although reconstitution occurs earlier after autologous HSCT than after allogeneic HSCT, the approaches to vaccination are the same. Efficacy data for vaccines in HSCT recipients are limited.

Vaccination in accordance with transplant centre-specific immunization guidelines is generally part of routine post-transplant care provided by the transplant centres.

Pre-HSCT immunization

If time permits, careful consideration must be given to the pre-transplant immunization status of the HSCT candidate. All routine non-live vaccines should be given as appropriate for age. In addition, conjugate pneumococcal vaccine (regardless of age) and polysaccharide pneumococcal vaccine (if age 2 years or more) should be given if not previously received. If the transplant is planned during the influenza season, non-live influenza vaccine should be given. Non-live vaccines should be given at least 2 weeks prior to onset of the pre-transplant conditioning regimen. Live vaccines should not be given within 4 weeks of the start of conditioning. BCG should not be given at any time to those with a condition that will likely eventually require HSCT. BCG may persist in the body for at least a few years, and perhaps indefinitely, so there is a theoretical risk of reactivation post-transplant.

Donor vaccination may improve responses of the HSCT recipient to some vaccines; however, due to logistical and ethical issues it is often not feasible. When the HSCT donor is related to the recipient, consideration should be given to immunizing the donor before stem cell collection. As a minimum, the donor should have received all routine age-appropriate vaccines including routine boosters, COVID-19 vaccines, and influenza vaccine if stem cell collection is to occur during the influenza season. Non-live vaccines should be given at least 2 weeks prior to stem cell collection. Live parenteral vaccines are contraindicated within 4 weeks of stem cell collection. For autologous HSCT, non-live vaccines should be given at least 2 weeks before and live parenteral vaccines at least 4 weeks before stem cell collection.

If indicated for age and by immune status, and if feasible, a primary series of a non-live COVID-19 vaccine should be completed at least 2 weeks prior to onset of the pre-transplant conditioning regimen for allogeneic HSCT and at least 2 weeks prior to stem cell collection for autologous HSCT.

Doses of COVID-19 vaccine may be given at an interval shorter than the recommended interval of 8 weeks, respecting the minimum authorized interval.

If the recipient or donor is eligible for a booster dose, consideration should be given to administering the booster at least 2 weeks prior to stem cell collection, if feasible.

At this time, it is not known if giving an extra dose of COVID-19 vaccine prior to conditioning or stem cell collection would improve response to COVID-19 vaccine post-HSCT.

If transplantation is urgent, it should not be delayed to facilitate donor or recipient vaccination.

Post-HSCT immunization

HSCT recipients should be viewed as "never immunized" and require re-immunization after transplant because the ablation of hematopoietic cells in the bone marrow pre-transplant eliminates most or all immune memory. In addition, certain vaccine preventable diseases pose increased risk for HSCT recipients of all ages (e.g., pneumococcus, Hib, measles, varicella, and influenza). HSCT recipients respond poorly to polysaccharide vaccines, such as pneumococcal polysaccharide 23-valent vaccine. If serologic testing is available and there is a clear antibody correlate of protection, measurement of post-immunization antibody titres to determine immune response and guide re-vaccination and post-exposure management should be considered.

Non-live vaccines

All routine non-live vaccines should be given (or repeated) for HSCT recipients generally beginning 6 to 12 months post-transplant (pneumococcal conjugate vaccine may be given beginning at 3 to 6 months post-transplant, non-live influenza vaccine may be given beginning at 4 to 6 months post-transplant). Pneumococcal conjugate vaccine and Hib vaccine should be given regardless of age. Those 2 years of age or older should receive pneumococcal polysaccharide vaccine at 12 to 18 months post-transplant (6 to 12 months after the last dose of pneumococcal conjugate vaccine) if no GVHD. Hepatitis B vaccine should be given at double the dose used in the routine 3-dose schedule. HPV vaccine should be given using a 3-dose schedule, regardless of age. For individuals with increased risk of meningococcal disease because of underlying medical conditions (e.g., functional hyposplenia), quadrivalent conjugate meningococcal is recommended and serogroup B meningococcal vaccine should be offered. Meningococcal vaccines are also recommended for individuals at increased risk of exposure to meningococcal disease (e.g., from travel or occupation).

The primary series (initial or repeat) of COVID-19 vaccine should be initiated 3 to 6 months after HSCT. In general, it is recommended that the immunization of immunocompromised persons occur at a time when the immune response can be maximized. However, delaying COVID-19 vaccination to maximize the immune response needs to be weighed against the risk of infection while waiting, taking into consideration risk of exposure and local transmission of SARS-CoV-2. Time of initiation should also take into account the immune status of the HSCT recipient, including B-lymphocyte counts, receipt of immunosuppressive therapy currently or within the past 3 months, rituximab therapy or other anti-B cell monoclonal antibody within the last 12 months, and active GVHD or moderate to severe cGVHD.

Individuals with recent or current immunosuppressive therapy or active cGVHD are expected to have lower seroconversion rates, but nevertheless, rates of 56%, 63% and 73% have been reported in HSCT recipients on immunosuppression. New cGVHD and worsening of cGVHD have occasionally been reported after receipt of a COVID-19 vaccine, but whether or not vaccination was causal is not known. Patients at risk for GVHD should be advised that a cGVHD flare may occur but relationship to the vaccine is unknown. Careful monitoring of patients with a history of cGVHD is warranted. If new onset or exacerbation of GVHD occurs after COVID-19 vaccination, the decision to give a further dose should be made on an individual basis, taking into consideration risk of exposure to SARS-CoV-2 and the severity of the GVHD.

Live attenuated vaccines

MMR and univalent varicella vaccines may be considered 24 months or more post-transplant provided there is no evidence of chronic GVHD, immunosuppression has been discontinued for at least 3 months, the underlying disease for which the transplant was done (if immunosuppressive), is not active, and the person is considered immunocompetent by a transplant specialist. Yellow fever vaccine may be given if the above criteria are met and travel to an area with risk of yellow fever acquisition cannot be avoided. Other live vaccines are contraindicated. Note that some HSCT recipients may be receiving regular doses of immunoglobulin which will interfere with the response to live vaccines, in which case these vaccines (excluding yellow fever), should be deferred until 8-11 months after the last dose of immunoglobulin.

Refer to Table 3 and vaccine-specific chapters in Part 4 for recommendations for HSCT recipients.

Table 3: Post-transplantation vaccination of hematopoietic stem cell transplantation (HSCT) recipients
Vaccine	Post-transplantation	Comments
Non-live vaccines
Cholera and travellers' diarrhea (inactivated)	Use if indicated	Beginning 6 months post-HSCT
COVID-19^{Footnote 1}	Recommended: 3 doses and booster(s)	Beginning 3 to 6 months post-HSCT
Diphtheria^{Footnote 2}	Recommended: 3 doses	Beginning 6 to 12 months post-HSCT
Haemophilus influenzae type b (Hib)^{Footnote 3}	Recommended: 3 doses	Beginning 6 to 12 months post-HSCT
Hepatitis A	Use if indicated	Beginning 6 months post-HSCT Pre-exposure prophylaxis for travel: consider Ig with hepatitis A vaccine unless receiving routine IG replacement therapy. Post-exposure prophylaxis: Ig recommended along with hepatitis A vaccine unless receiving routine IG replacement therapy.
Hepatitis B	Recommended: 3 or 4 doses. Use double the routine dose if already immunocompromised	Beginning 6 to 12 months post-HSCT Double the routine dose; 3 or 4 dose schedule recommended Post-immunization monitoring of anti-HBs titres recommended with booster dose if titre less than 10 IU/L^{Footnote 4}
Herpes zoster (non-live recombinant)	Consider if indicated by age^{Footnote 5}
HPV	Recommended if indicated by age: 3 doses	Beginning 6 to 12 months post-HSCT; 3 dose schedule
Influenza (inactivated or recombinant)	Recommended annually 2 doses the first year post transplant if less than 9 years old	Beginning 4 to 6 months post-HSCT
Japanese encephalitis	Use if indicated	Beginning 6 months post-HSCT
Meningococcal, conjugate	Routine use. Use quadrivalent conjugate meningococcal vaccine if indicated^{Footnote 6}	Beginning 6 months post-HSCT
Meningococcal, serogroup B	Should be offered if indicated^{Footnote 6}	Beginning 6 months post-HSCT
Pertussis^{Footnote 2}	Recommended: 3 doses for children and adolescents up to age 18 1 dose for adults 18 years of age and older	Beginning 6 to 12 months post-HSCT
Pneumococcal conjugate 13-valent (Pneu-C-13)	Recommended: 3 doses, regardless of age	Beginning 3 to 6 months post-HSCT 3 doses of Pneu-C-13 vaccine at least 4 weeks apart
Pneumococcal polysaccharide (Pneu-P-23)	Recommended: 1 dose	Give 12 to 18 months post-HSCT if no GVHD (6 to 12 months after the last dose of Pneu-C-13) If GVHD, give 4th dose of Pneu-C-13 and delay polysaccharide until GVHD resolved Consider re-immunization after 1 year
Polio (inactivated)^{Footnote 2}	Recommended: 3 doses	Beginning 6 to 12 months post-HSCT
Rabies	Use if indicated	Do not use intradermally Give as needed for post-exposure management Use 5 dose schedule for post-exposure prophylaxis Beginning 6 to 12 months post-HSCT for pre-exposure prophylaxis Post-immunization serology recommended
Tetanus^{Footnote 2}	Recommended: 3 doses	Beginning 6 to 12 months post-HSCT
Typhoid (inactivated)	Use if indicated	Beginning 6 months post-HSCT
Live vaccines
Bacille Calmette-Guérin (BCG)	Contraindicated
Influenza (live)	Not recommended - use non-live vaccine
Measles-mumps-rubella	Recommended: 2 doses^{Footnote 7}	Beginning 24 months post-HSCT Serology recommended after 2nd dose
MMRV	Contraindicated
Rotavirus	Contraindicated
Smallpox	Contraindicated
Typhoid (live)	Contraindicated - if indicated use inactivated
Varicella (univalent)	Recommended: 2 doses^{Footnote 7}	Beginning 24 months post-HSCT Serology recommended after 2nd dose
Yellow fever	May be given if indicated^{Footnote 7}	Beginning 24 months post-HSCT
Abbreviations: anti-HBs antibody to hepatitis B surface antigen Ig immunoglobulin Footnote 1 For preferred type of COVID-19 vaccine, intervals between doses, and booster dose recommendations, refer to the COVID-19 vaccine chapter (https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-26-covid-19-vaccine.html). Return to footnote 1 referrer Footnote 2 Given as combined vaccine (diphtheria, tetanus, pertussis; ± polio, Hib depending on age and previous vaccine history). Return to footnote 2 referrer Footnote 3 May be given as a combined vaccine. Return to footnote 3 referrer Footnote 4 Initially annual monitoring of antibody levels may be considered. Optimal timing and frequency should be based on the severity of the immunocompromised state and the ongoing risk of acquisition of HB infection. Return to footnote 4 referrer Footnote 5 Non-live recombinant zoster vaccine may be considered in immunocompromised adults ≥ 50 years of age on a case by case basis. Data on the use in immunocompromised individuals is limited, but based on the burden of zoster illness in this population and the general safety of inactivated vaccines, the benefits of vaccination are expected to outweigh the risks. Return to footnote 5 referrer Footnote 6 Indicated for individuals at increased risk of meningococcal disease because of underlying medical conditions, or individuals at increased risk of exposure to meningococcal disease. Refer to Meningococcal Vaccine (https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-13-meningococcal-vaccine.html) in Part 4 for additional information on high risk individuals. Return to footnote 6 referrer Footnote 7 Give when immunosuppression has been discontinued for at least 3 months, no chronic GVHD, no Ig in the past 8 to 11 months (except for yellow fever vaccine) and considered immunocompetent by a transplant specialist. Return to footnote 7 referrer

Solid organ transplantation

Solid organ transplant recipients are at increased risk of severe illness with many vaccine preventable diseases, including invasive pneumococcal or Hib disease, influenza, varicella, and HPV-related diseases.

Pre-solid organ transplantation

Pre-transplant immunization is routine at most transplant centres. Ideally, all non-immune solid organ transplantation candidates should be immunized prior to transplantation and as early in the course of disease as possible because vaccine response may be reduced in people with organ failure pre-transplant. In addition, vaccines are more immunogenic if given before transplantation because the immunosuppressive medications given after transplant to prevent and treat rejection of the transplanted organ may diminish the vaccine response. It is especially important that live vaccines are given pre-transplant if possible, as these will be contraindicated post-transplant. MMR and varicella vaccine may be given to infants 6-11 months of age if transplantation is expected to occur before age 12 months. If transplantation is delayed, repeat doses should be given starting at one year of age.

Non-live vaccines should be given according to routine immunization schedules, with the exceptions that hepatitis B vaccine should be given at double the usual dose using a 3- or 4-dose schedule if on dialysis or immunocompromised. If immunocompromised, HPV vaccine should be given using a 3-dose schedule regardless of age. In general, routine age indications should be followed, however HPV vaccination may be considered prior to an imminent transplantation in a 7- or 8-year-old child, recognizing that there is no immunogenicity data for this age group. The risk of HPV-associated warts is high post-transplant; HPV 9- or 4-valent vaccine will provide additional protection over that of the 2-valent vaccine. In addition, transplant candidates should receive pneumococcal conjugate vaccine regardless of age, pneumococcal polysaccharide vaccine if 2 years of age or older, and one dose of Hib vaccine after age 5 years regardless of prior Hib vaccination history.

Non-live influenza vaccine should be given annually. Hepatitis A vaccine is indicated for liver transplant candidates and others with risk factors for hepatitis A. For individuals with increased risk of meningococcal disease because of underlying medical conditions, quadrivalent conjugate meningococcal is recommended and serogroup B meningococcal vaccine should be offered. Meningococcal vaccines are also recommended for individuals at increased risk of exposure to meningococcal disease (e.g., from travel or occupation).

Non-live vaccines should be given at least 2 weeks before transplantation and live attenuated vaccines (MMR, MMRV, varicella, rotavirus, LAIV) should be given at least 4 weeks prior to transplantation. BCG may persist in the body for at least a few years, and perhaps indefinitely. It should not be given to any patient who is anticipated to likely need an organ transplant in the future, unless potential benefit outweighs the risk of reactivation post-transplant.

Antibody response should be determined by serology for those vaccines with an antibody correlate of immunity available. For infants less than 18 months of age, presence of passive maternal antibody must be considered.

Refer to Table 4 and vaccine-specific chapters in Part 4 for recommendations for vaccination of solid organ transplant candidates.

Living donors should have received all age-appropriate vaccines. Live vaccines should not be given in the 4 weeks before organ procurement.

Post-solid organ transplantation

Solid organ recipients generally receive lifelong immunosuppression, which varies substantially depending on the organ transplanted. Usually the degree of immune suppression is greatest in the first 3 to 6 months post-transplant, although this timeline varies if treatment for acute organ rejection is required. In the absence of this later scenario, immune suppression typically progresses to the maintenance phase between 6 months -1 year, but a significant degree of immune suppression persists indefinitely. A minority of transplant recipients who experience chronic rejection, persistent organ dysfunction, or chronic infections, remain profoundly immune suppressed.

Non-live vaccines

In general, vaccination with non-live vaccines should not be re-initiated until maintenance immunosuppression is attained. Recommended non-live vaccines that were not given pre-transplant and recommended booster doses should be given. Hepatitis B vaccine should be given at double the usual dose and using a 3-dose or 4-dose schedule. HPV vaccine should be given following routine age indications but using a 3-dose schedule, regardless of age.

If serologic testing is available and there is a clear antibody correlate of protection, measurement of post-immunization antibody titres to determine immune response and guide re-vaccination and post-exposure management should be considered.

Live attenuated vaccines

Live vaccines are generally contraindicated after transplant. However, univalent varicella vaccine has been given to selected pediatric renal and liver transplant recipients without recent graft rejection and receiving minimal or no immune suppression; consultation with an expert is advised regarding varicella vaccination of non-immune organ transplant recipients.

Most newly transplanted solid organ recipients receive vaccination in accordance with transplant centre-specific immunization guidelines as part of routine post-transplant care.

Refer to Table 4 and vaccine-specific chapters in Part 4 for recommendations for vaccination of solid organ transplant recipients.

Table 4: Vaccination of solid organ transplant candidates and recipients
Vaccine	Pre-transplant^{Footnote 1}^{Footnote 2}	Post-transplant (if not completed pre-transplant)	Comments
Non-live vaccines^{Footnote 2}
Cholera and travellers' diarrhea (inactivated)	Use if indicated	Use if indicated
Diphtheria^{Footnote 3}	Routine use^{Footnote 4}	Routine use^{Footnote 4}
Haemophilus influenzae type b (Hib)^{Footnote 5}	Children less than 5 years of age: routine use Individuals 5 years of age and older: 1 dose recommended^{Footnote 6}	Children less than 5 years of age: routine use Individuals 5 years of age and older: 1 dose recommended^{Footnote 6}
Hepatitis A	Recommended for liver transplant candidates and others with chronic liver disease Otherwise, use if indicated	Recommended for liver transplant recipients and others with chronic liver disease Otherwise, use if indicated	Post-transplant: Pre-exposure prophylaxis for travel: consider Ig with hepatitis A vaccine Post-exposure prophylaxis: Ig recommended along with hepatitis A vaccine
Hepatitis B	Recommended	Recommended	Double the routine dose and 3 or 4-dose schedule recommended post-transplant, and pre-transplant if on hemodialysis or otherwise immunocompromised Post-immunization monitoring of anti-HBs titres recommended with booster dose if titre less than 10 IU/L^{Footnote 7}
Herpes zoster (non-live recombinant)	Consider if indicated by age^{Footnote 8}	Consider if indicated by age^{Footnote 8}
HPV	Routine use	Routine use	3 dose schedule recommended May be considered for pre-transplant administration prior to routinely recommended age, if reasonably close to minimum recommended age for vaccination
Influenza (inactivated or recombinant)	Recommended annually	Recommended annually
Japanese encephalitis	Use if indicated	Use if indicated
Meningococcal, conjugate	Routine use. Use quadrivalent conjugate meningococcal vaccine if indicated^{Footnote 9}	Routine use Use quadrivalent conjugate meningococcal vaccine if indicated^{Footnote 9}
Meningococcal, serogroup B	Should be offered if indicated^{Footnote 9}	Should be offered if indicated^{Footnote 9}
Pertussis^{Footnote 3}	Routine use	Routine use
Pneumococcal conjugate 13-valent	Recommended regardless of age	Recommended regardless of age	Should be followed, at age at least 2 years and at least 2 months after last dose, with pneumococcal polysaccharide vaccine^{Footnote 10}
Pneumococcal polysaccharide	Recommended if 2 years of age or older	Recommended if 2 years of age or older	One life-time re-immunization recommended, 5 years after first dose
Polio (inactivated)^{Footnote 3}	Routine use	Routine use
Rabies	Use if indicated	Use if indicated	Do not use intradermally Use 5 dose schedule for post-exposure prophylaxis Post-immunization serology recommended
Tetanus^{Footnote 3}	Routine use	Routine use
Typhoid (inactivated)	Use if indicated	Use if indicated
Live attenuated vaccines^{Footnote 11}
Bacille Calmette-Guérin (BCG)	Contraindicated unless potential benefit outweighs the risk^{Footnote 12}	Contraindicated
Influenza (live)	Use if indicated	Not recommended; use non-live vaccine
Measles-mumps-rubella	Recommended^{Footnote 13}	Not recommended	Complete 2-dose series 4 weeks or more pre-transplant Post-immunization serology recommended
MMRV	Recommended if age appropriate ^{Footnote 13}	Not recommended	Complete 2-dose series 4 weeks or more pre-transplant Post-immunization serology recommended
Rotavirus	Routine use	Not recommended
Smallpox	Contraindicated	Contraindicated
Typhoid (live)	Use if indicated	Contraindicated; if indicated, use non-live vaccine
Varicella	Recommended^{Footnote 13}	Not recommended	Complete 2-dose series 4 weeks or more pre-transplant Consider post-immunization serology
Yellow fever	Use if indicated	Contraindicated
Abbreviations: anti-HBs antibody to hepatitis B surface antigen Ig immunoglobulin Footnote 1 Whenever possible, vaccine series should be completed pre-transplantation. Vaccines given post-transplant may not be sufficiently immunogenic. Return to footnote 1 referrer Footnote 2 Non-live vaccines should be given at least 2 weeks before transplantation and, in general, should not be given post-transplant until baseline immunosuppression levels are attained. Return to footnote 2 referrer Footnote 3 Given as combined vaccine (diphtheria, tetanus, pertussis; ± polio, Hib depending on age and previous vaccine history). Return to footnote 3 referrer Footnote 4 Routine use: follow routine immunization schedules with age-appropriate booster doses. Return to footnote 4 referrer Footnote 5 May be given as combined vaccine. Return to footnote 5 referrer Footnote 6 Regardless of prior history of Hib vaccination and at least 1 year after any previous dose. Return to footnote 6 referrer Footnote 7 Initially annual monitoring of antibody levels may be considered. Optimal timing and frequency should be based on the severity of the immunocompromised state and the ongoing risk of acquisition of HB infection. Return to footnote 7 referrer Footnote 8 Non-live recombinant zoster vaccine may be considered in immunocompromised adults ≥ 50 years of age on a case by case basis. Data on the use in immunocompromised individuals is limited, but based on the burden of zoster illness in this population and the general safety of inactivated vaccines, the benefits of vaccination are expected to outweigh the risks. Return to footnote 8 referrer Footnote 9 Indicated for individuals at increased risk of meningococcal disease because of underlying medical conditions, or individuals at increased risk of exposure to meningococcal disease. Refer to Meningococcal Vaccine (https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-13-meningococcal-vaccine.html) in Part 4 for additional information on high risk individuals. Return to footnote 9 referrer Footnote 10 Pneu-C-13 vaccine followed by Pneu-P-23 vaccine is recommended. Antibody titres decline after 3 years; however, experience with re-immunization with Pneu-C-13 after solid organ transplant is limited. Return to footnote 10 referrer Footnote 11 Live attenuated vaccines should be given at least 4 weeks prior to transplantation. Return to footnote 11 referrer Footnote 12 BCG may remain in the body for at least a few years, and perhaps indefinitely. Use only if benefit outweighs potential risk of reactivation post-transplant. Return to footnote 12 referrer Footnote 13 MMR and univalent varicella vaccine may be given to infants as early as 6 months of age if transplantation is anticipated before 12 months of age. If transplantation is delayed, repeat doses should be given starting at one year of age. MMRV not recommended for age < 12 months at this time. Return to footnote 13 referrer

Immunosuppressive therapy

Long-term immunosuppressive therapy is used for various disease conditions including cancer, organ transplantation, GVHD following HSCT, and chronic inflammatory conditions (e.g., inflammatory bowel disease, inflammatory arthritis, psoriasis, systemic lupus erythematosus). Therapies include cancer chemotherapy, radiation therapy, long term high-dose steroid treatment (prednisone equivalent of ≥ 2 mg/kg/day or 20 mg/day if weight > 10 kg, for ≥ 14 days), cytotoxic drugs, calcineurin inhibitors, chimeric antigen receptor (CAR) T cell therapy targeting lymphocytes, biological response modifiers and antibodies that target lymphocytes.

Most of these therapies have their greatest impact on cell-mediated immunity, although T cell-dependent antibody production can also be adversely affected. Monoclonal antibodies that deplete B cells profoundly affect antibody production; this effect can last for several months or years following completion of therapy. The nature of the person's underlying disease should also be considered.

CAR T cell cancer immunotherapy involves reprogramming a patient’s own T cells to identify and eliminate malignant cells. The patient’s T cells are obtained, modified in a laboratory, then infused back into the individual. Commercial CAR T cells from allogeneic donors are also available. CAR T cell therapy is used most frequently to treat hematologic malignancies, especially of B cell origin (e.g., CD19). This therapy eliminates malignant as well as normal cells expressing the target antigen, resulting in profound and prolonged loss of B lymphocytes and thus antibody production.

In general, if a patient is 3 months post-chemotherapy and the cancer is in remission, or if immunosuppression has been discontinued for at least 3 months (6 months or more for anti-B cell antibodies or CAR T cells targeting lymphocytes), the person is no longer considered immunocompromised.

Prior to immunosuppressive therapy

Vaccination status should be reviewed for immunocompetent persons who might be anticipating initiation of immunosuppressive treatments or who have diseases that might lead to immunodeficiency. Ideally, all appropriate routine vaccines or boosters should be administered before the initiation of immunosuppressive therapy so that optimal immunogenicity is achieved. Although non-live vaccines can be safely administered at any time before, during or after immunosuppression, non-live vaccines should be administered at least 14 days before initiation of immunosuppressive therapy to optimize immunogenicity. Live vaccines should be administered at least 4 weeks before immunosuppressive therapy is started to reduce the risk of disease caused by the vaccine strain.

People undergoing immunosuppressive therapy are at higher risk of invasive pneumococcal disease and influenza-related complications; therefore, in addition to routine vaccines they should receive conjugate pneumococcal vaccine regardless of age and polysaccharide pneumococcal vaccine if aged 2 years or more, as well as annual immunization with non-live influenza vaccine. Hib vaccine may be recommended in some circumstances, such as following organ transplants.

Refer to vaccine-specific chapters in Part 4 for additional information.

During or after immunosuppressive therapy

If immunization cannot be completed prior to initiation of immunosuppressive therapy, generally a period of at least 3 months should elapse between therapy cessation and the administration of non-live vaccines (if possible, to ensure maximum immunogenicity) or live vaccines (to reduce the risk of disease caused by the vaccine strain). However, this interval may vary with the type and intensity of treatment, underlying disease, or urgency of vaccination if vaccines are needed for post-exposure or outbreak management. For example, whereas immunization can occur as early as 4 weeks following discontinuation of long term high-dose systemic steroid therapy, a longer interval of 6 to 12 months or more may be required in case of therapy with rituximab (or other monoclonal anti-B cell antibody) and some other biological response modifiers. B cell enumeration is generally performed during rituximab therapy and should be reviewed prior to immunization.

Recipients of CAR T cell therapy directed against lymphocytes should be regarded as “never immunized” and managed as HSCT recipients are. The primary series (initial or repeat) of non-live vaccines, including COVID-19 vaccines which should be initiated 3 to 6 months after CAR T cell therapy. Antibody response is unlikely while B cell aplasia persists, but cellular responses may occur.

Live vaccines may be given immediately on discontinuation of high dose steroid therapy if duration was less than 14 days. Corticosteroid therapy is not a contraindication to immunization with live vaccines when steroid therapy is short-term (i.e., less than 14 days); or low-to-moderate dose (prednisone equivalent of less than 2 mg/kg/day or less than 20 mg/day if weight > 10 kg); or physiologic replacement therapy; or administered topically, inhaled, or locally injected (e.g., joint injection). An exception is LAIV, which is contraindicated in individuals with severe asthma who are currently receiving high dose inhaled steroids.

For recipients of therapy with long term effects on the immune system, such as CAR T directed against lymphocytes, anti-B cell antibody, and some other biological response modifiers, live vaccines should not be given until adequate immune reconstitution has been confirmed by an expert.

The following principles apply if immunosuppressive therapy cannot be stopped.

Non-live vaccines

Non-live vaccines (as indicated under “Prior to immunosuppressive therapy”, above) may be administered if needed during immunosuppression. If risk of exposure is low, non-live vaccines may be temporarily delayed until the person is the least immunosuppressed. Doses may need to be repeated when the person is no longer immunosuppressed unless antibody response can be demonstrated. Hepatitis B vaccine should be given at double the usual dose and using a 3- or 4-dose schedule. HPV vaccine should be given following routine age indications but using a 3-dose schedule, regardless of age. Non-live influenza vaccine should be given during influenza season except for those on induction chemotherapy for leukemia or receiving anti-B cell antibodies, who are unlikely to respond. If zoster vaccine is indicated, non-live recombinant zoster vaccine should be considered.

Live attenuated vaccines

Live vaccines are generally contraindicated. Because immunosuppressive drugs have been reported to cause reactivation of latent tuberculosis infection and predisposition to other opportunistic infections, avoidance of live vaccines during high level immunosuppressive therapy is prudent.

The safety and efficacy of live vaccines during low dose intermittent or maintenance therapy with non-corticosteroid immunosuppressive drugs are generally unknown, with the exception of varicella vaccine, which can be considered for those receiving low dose methotrexate (≤ 0.4 mg/kg/week); azathioprine (≤ 3 mg/kg/day), or 6-mercaptopurine (≤ 1.5 mg/kg/day). If combination low dose immunosuppression is being used, an expert should be consulted. A careful risk benefit assessment should be done if other live attenuated vaccines are to be considered in patients on low dose immunosuppression.

Infants exposed to immunosuppressive therapy in the womb

Special consideration should be given to immunizing infants who have been exposed to monoclonal antibodies in the womb. Some monoclonal antibodies taken during pregnancy can, similar to maternal antibodies, pass through the placental barrier, potentially resulting in various forms of temporary immunosuppression in infants. For example, rituximab taken during pregnancy is associated with B-cell depletion in both mother and fetus, while infliximab can be detected in infants up to 6 months after birth.

Due to the potential risk of disseminated disease, administration of BCG and oral polio vaccines is contraindicated in such infants who are less than 6 months of age. A longer interval of 6-12 months should be observed following rituximab therapy. Oral polio vaccine is no longer used in Canada but continues to be used in some other countries.
There are no data at this time regarding the potential risk associated with rotavirus (RV) vaccine in these infants. Prior to RV immunization, laboratory tests may be useful in assessing humoral and cellular immune status. When considering immunization in the absence of laboratory test results, the decision to immunize should be based on an individual risk-benefit assessment. For example, in jurisdictions with ongoing RV immunization programs, indirect protection through herd immunity is likely to be high and withholding immunization may be considered until more information about the effects of monoclonal antibodies in the womb becomes available. Alternatively, in jurisdictions that do not have RV immunization programs and where exposure to wild-type rotavirus may be high, immunization with RV vaccine may be prudent to reduce the risk of potential complications from RV infection.
Immune responses to live vaccines that are administered at or after one year of age (e.g., MMR or MMRV vaccine) are not considered to be affected by exposure to monoclonal antibodies in the womb.
Infants exposed to monoclonal antibodies in the womb should receive all non-live vaccines according to routine schedule, keeping in mind that immune response during the first few months may be suboptimal, depending on the monoclonal used and the gestational period during which it was administered.

Monoclonal antibodies administered to the mother during breastfeeding are thought to have very little or no impact on the infant. Transfer of monoclonal antibodies through breast milk is limited, and the minimal quantities that are ingested are likely to be broken down in the infant’s gastrointestinal tract. Infants of breastfeeding women receiving monoclonal antibody treatment post-partum should therefore be immunized with both live and non-live vaccines according to routine schedules, unless the infant was also exposed to monoclonal antibody in the womb.

Refer to vaccine-specific chapters in Part 4 for additional information.

HIV infection

The degree of immune suppression varies widely among HIV-infected individuals, reflecting disease stage and response to antiretroviral therapy. Immune suppression is approximately predicted by a recent CD4 count and CD4 percentage.

Children who are immune suppressed at HIV diagnosis and have already received routine vaccines should have antibody titres measured where possible and, if indicated, should be revaccinated after immune recovery.

Non-live vaccines

When possible, vaccines should be given early in the course of HIV infection although there is no contraindication to the use of non-live vaccines at any time. If immune suppression is severe in an untreated or newly treated patient and likelihood of exposure to the vaccine-preventable disease is low, vaccination may be deferred pending immune recovery after effective antiretroviral therapy.

Non-live vaccines should be administered to HIV-infected people according to routine immunization schedules, with the exceptions that hepatitis B vaccine should be given at double the routine dose and using a 3 or 4 dose schedule. HPV vaccine should be given following routine age indications but using a 3 dose schedule regardless of age. There is a high risk of HPV-associated warts with HIV infection; HPV 9 or 4 valent vaccine will provide additional protection over that of the 2 valent vaccine. For those 6 months of age or older, annual immunization with non-live influenza vaccine is recommended. HIV-infected people should also receive pneumococcal conjugate vaccine regardless of age, pneumococcal polysaccharide vaccine if 2 years of age or older, and one dose of Hib vaccine after age 5 years regardless of prior Hib vaccination. Quadrivalent conjugate meningococcal vaccine is recommended and serogroup B meningococcal vaccine should be offered. Booster doses of quadrivalent conjugate meningococcal vaccine are recommended every 3 to 5 years depending on age of initial vaccination. For serogroup B meningococcal vaccines, the timing of booster doses is yet to be determined. Hepatitis A vaccine is recommended for those with risk factors for hepatitis A acquisition. If herpes zoster vaccine is indicated by age, non-live recombinant zoster vaccine should be considered.

Live attenuated vaccines

The risks and benefits of a live vaccine need to be carefully considered in consultation with an infectious disease specialist/immunologist.

In general, infants should receive rotavirus vaccine according to routine schedule, as risk from infection with wild strain outweighs theoretical risk from the vaccine. If the infant is known to have severe immunodeficiency, consultation with a specialist is recommended.

MMR and varicella vaccines may be considered early in the course of HIV-infection if immune function is normal. Although LAIV is generally contraindicated, studies have shown it to be safe and immunogenic and many experts would consider using it for HIV-infected children on antiretroviral therapy and with normal immune function (see below). MMRV and other live vaccines are contraindicated at this time because of lack of data on safety. If immune suppression is already advanced at diagnosis, live vaccines should be deferred pending potential immune recovery with treatment. Consensus thresholds based on immunologic categories have been determined for the use of MMR, univalent varicella and LAIV as follows:

Asymptomatic HIV-infected children 12 months of age and older without severe immunosuppression (i.e., CD4 ≥ 15% and CD4 cell count ≥ 500 × 10⁶/L for at least 6 months in children 1 through 5 years old and ≥ 15% and CD4 cell count ≥ 200 × 10⁶/L for at least 6 months in those 6 through 13 years of age) may receive MMR and univalent varicella vaccines.
Immunization with MMR may be considered for susceptible HIV-infected adolescents and adults with CD4 cell count ≥ 200 × 10⁶/L. There are no published data on the use of varicella vaccine in susceptible HIV-infected adults. HIV-infected adults should be asked for a history of varicella disease or vaccination, and if negative for both, serology should be requested to determine susceptibility. Based on expert opinion, varicella immunization may be considered for susceptible HIV-infected adults with CD4 cell count ≥200 × 10⁶/L.
If MMR or varicella vaccines were given to individuals with perinatal HIV infection before antiretroviral therapy was begun and serological response is not demonstrated, doses should be repeated once on effective therapy for at least 6 months.
Live attenuated influenza vaccine may be considered in otherwise healthy HIV-infected patients aged 5–17 years on combination antiretroviral therapy regimen for ≥16 weeks with CD4 T-lymphocyte percentage ≥15 and HIV plasma RNA <60 000 copies.

Refer to Table 5 for recommendations for vaccination of HIV-infected persons and vaccine-specific chapters in Part 4 for additional information.

Table 5: Vaccination of HIV-infected persons
Vaccine	Recommendation	Comments
Non-live vaccines
Cholera and travellers' diarrhea (inactivated)	Use if indicated
Diphtheria^{Footnote 1}	Routine use^{Footnote 2}
Haemophilus influenzae type b (Hib)^{Footnote 3}	Children less than 5 years of age: routine use Individuals 5 years of age and older: 1 dose recommended ^{Footnote 4}
Hepatitis A	Use if indicated	Recommended for HIV-infected individuals with risk factors such as chronic liver disease including HBV or HCV infection, living in a community where hepatitis A is endemic, men who have sex with men or disordered use of substances Pre-exposure prophylaxis for travel: consider Ig with hepatitis A vaccine Post-exposure prophylaxis: Ig recommended along with hepatitis A vaccine unless immune function is normal
Hepatitis B	Recommended	Double the usual dose is recommended Post-immunization monitoring of anti-HBs titres recommended with booster dose if titre less than 10 IU/L^{Footnote 5}
Herpes zoster (non-live recombinant)	Consider if indicated by age^{Footnote 6}
HPV	Routine use	3-dose schedule recommended
Influenza (inactivated or recombinant)	Recommended annually
Japanese encephalitis	Use if indicated
Meningococcal, quadrivalent conjugate	Recommended	Administer from 2 months of age. Booster doses required every 3-5 years depending on age of initial vaccination.^{Footnote 7}
Meningococcal, serogroup B	Should be offered	Administer from 2 months of age.^{Footnote 8} The timing of booster doses has not yet been determined.
Pertussis^{Footnote 1}	Routine use
Pneumococcal conjugate 13-valent	Recommended regardless of age	Should be followed, at least 2 years of age and at least 2 months after last dose, with pneumococcal polysaccharide vaccine
Pneumococcal polysaccharide	Recommended if age 2 years or more	One re-immunization recommended, 5 years after first dose
Polio (inactivated)^{Footnote 1}	Routine use
Rabies	Use if indicated	Do not use intradermally Use 5 dose schedule for post-exposure prophylaxis Post-immunization serology recommended
Tetanus^{Footnote 1}	Routine use
Typhoid (inactivated)	Use if indicated
Live attenuated vaccines
Bacille Calmette-Guérin (BCG)	Contraindicated
Influenza (live)	Not recommended, use inactivated vaccine	Some experts advise that LAIV may be considered in otherwise healthy HIV-infected children on combination antiretroviral therapy regimen for ≥16 weeks with CD4 T-lymphocyte percentage ≥15 and HIV plasma RNA <60 000 copies ^{Footnote 9}
Measles-mumps-rubella	Children ≥ 12 months of age: Recommended 2 doses 3-6 months apart, if not significantly immunocompromised Adolescents and adults: consider 2 doses 3-6 months apart if susceptible and not significantly immunocompromised Contraindicated in advanced HIV/AIDS	Give if CD4 ≥ 15% and ≥ 500 x 10⁶ cells /L for at least 6 months if age less than 6 years; if CD4 ≥ 15% and ≥ 200 x 10⁶ cells /L for at least 6 months if age 6-13 years; if CD4 cell count ≥ 200 x 10⁶ cells /L if age ≥ 14 years. If given to an individual with perinatal HIV infection before antiretroviral therapy was begun and serological response is not demonstrated, doses should be repeated once on effective therapy for at least 6 months Consider post-immunization serology
MMRV	Contraindicated
Rotavirus	Routine use unless severely immunocompromised	If the infant is known to have severe immunodeficiency, consult a specialist in pediatric HIV or immunology
Smallpox	Contraindicated
Typhoid (live)	Contraindicated; if indicated, use inactivated vaccine
Varicella (univalent)	Children ≥ 12 months of age: Recommended 2 doses 3-6 months apart if not significantly immunocompromised Adolescents and adults: consider 2 doses 3-6 months apart if susceptible and not significantly immunocompromised Contraindicated in advanced HIV/AIDS	Give if CD4 cell count ≥ 15% and ≥ 500 x 10⁶ cells /L for at least 6 months if age less than 6 years and if CD4 cell count ≥ 15% and ≥ 200 x 10⁶ cells /L for at least 6 months if older If given to child with perinatal HIV infection before antiretroviral therapy was begun and serological response is not demonstrated, doses should be repeated once on effective therapy for at least 6 months Consider post-immunization serology
Yellow fever	May be considered if asymptomatic and not significantly immune compromised	May be considered if CD4 count greater than 200 x 10⁶/L (or if age 9 months - 5 years and asymptomatic with CD4 ≥ 15 %). Consult specialist in HIV infection / immunology. Vaccinate well in advance of travel to monitor potential adverse events Consider post-immunization serology
Abbreviations: HBV Hepatitis B virus HCV Hepatitis C virus anti-HBs antibody to hepatitis B surface antigen LAIV Live attenuated influenza vaccine Footnote 1 Given as combined vaccine (diphtheria, tetanus, pertussis; ± polio, Hib depending on age and previous vaccine history). Return to footnote 1 referrer Footnote 2 Routine use: follow routine immunization schedules with age-appropriate booster doses. Return to footnote 2 referrer Footnote 3 May be given as combined vaccine. Return to footnote 3 referrer Footnote 4 Regardless of prior history of Hib vaccination and at least 1 year after any previous dose. Return to footnote 4 referrer Footnote 5 Initially annual monitoring of antibody levels may be considered. Optimal timing and frequency should be based on the severity of the immunocompromised state and the ongoing risk of acquisition of HB infection. Return to footnote 5 referrer Footnote 6 Non-live recombinant zoster vaccine may be considered in immunocompromised adults ≥ 50 years of age on a case by case basis. Data on the use in immunocompromised individuals is limited, but based on the burden of zoster illness in this population and the general safety of non-live vaccines, the benefits of vaccination are expected to outweigh the risks. Return to footnote 6 referrer Footnote 7 Refer to Meningococcal Vaccine, Booster doses and re-immunization in Part 4 (https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-13-meningococcal-vaccine.html#booster) for additional information for re-vaccination recommendations and intervals. Return to footnote 7 referrer Footnote 8 4CMenB vaccine is indicated for immunization of high risk individuals greater than or equal to two months of age; MenB-fHBP vaccine may be considered as an option for use in high-risk individuals 10 years of age and older. Return to footnote 8 referrer Footnote 9 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014; 58(3):e44-100. Return to footnote 9 referrer

Close contacts

Annual influenza vaccine and up-to-date routine immunizations are recommended for household members and other close contacts of people with chronic diseases, as well as for their health care workers. Non-immunized close contacts of immunocompromised people should be immunized against pertussis, Hib, rotavirus, pneumococcus, measles, mumps, rubella, varicella, zoster and influenza as appropriate for age. Non-immune household or close contacts of immunocompromised people should be given hepatitis B vaccine. In addition, non-immune close contacts of HSCT recipients and close contacts of solid organ transplant candidates and recipients should receive hepatitis A vaccine if other risks for hepatitis A infection are present.

Vaccine viruses in MMR vaccine are not transmitted to contacts. Transmission of varicella vaccine virus from people with post-varicella vaccine rash occurs but is rare. Susceptible close contacts of immunocompromised people should receive MMR, MMRV, varicella or herpes zoster vaccine as appropriate for age. If the varicella vaccine recipient develops a varicella-like rash, the rash should be covered and the vaccinee should avoid direct contact with the immunocompromised person for the duration of the rash.

Infants living in households with persons who have or are suspected to have immunosuppressive conditions or who are receiving immunosuppressive medications can receive rotavirus vaccine. Following administration of rotavirus vaccine, viral antigen shedding in the stool may be detected in some vaccinees and may persist for up to 4 weeks. Transmission to household contacts occurs but is uncommon and many experts believe that the benefit of protecting immunocompromised household contacts from naturally occurring rotavirus by immunizing infants outweighs the theoretical risk of transmitting vaccine virus. To minimize the risk of transmission of vaccine virus during the 4 weeks after immunization, careful hand washing should be performed after contact with the vaccinated infant, especially after handling feces (e.g., after changing a diaper), and before food preparation or direct contact with the immunocompromised person.

Annual influenza immunization with influenza vaccine is recommended for close contacts of immunocompromised persons. Because of the theoretical risk for transmission, recipients of live attenuated influenza vaccine should avoid close association with persons with severe immunocompromising conditions (e.g., hematopoietic stem cell transplant recipients requiring isolation in hospital) for at least 2 weeks following vaccination.

Oral polio vaccine should not be administered to household contacts of an immunocompromised person. If there are household contacts who have received live, oral polio vaccine in another country within the last 6 weeks, they should not have contact with immunocompromised persons. Oral polio vaccine is not available in Canada.

Smallpox vaccine is available in Canada only for selected personnel working with vaccinia virus in research laboratories, or if an exposure to smallpox were to occur. Generally, smallpox vaccine should not be administered to household or close contacts of an immunocompromised person in a non-emergency situation. If vaccination is required in an outbreak situation, precautions should be taken to prevent spread to the immunocompromised person and other household and close contacts.

Immunocompromised travellers

A growing number of Canadians with reduced immune competence are travelling to tropical and low-income countries. Although the degree and range of infectious disease risks can increase significantly when an immunocompromised individual travels to other countries, the principles outlined above apply.

Travellers may require additional vaccines, depending on their destinations. Some travel vaccines may be contraindicated in immunocompromised individuals.

For additional information about immunization of immunocompromised travellers, refer to the Committee to Advise on Tropical Medicine and Travel statement on The immunocompromised traveller, vaccine-specific chapters in Part 4 and Immunization of travellers in Part 3.

Selected references

Abid, MA, Abid MB. SARS-CoV-2 vaccine response in CAR T-cell therapy recipients: A systematic review and preliminary observations. Hematological Oncology 10.1002/hon.2957. 15 Dec. 2021, doi:10.1002/hon.2957. https://onlinelibrary.wiley.com/doi/10.1002/hon.2957
Alashkar F., Vance C., Herich-Terhurne D., Preising N., Duhrsen U., Roth A. Serologic response to meningococcal vaccination in patients with paroxysmal nocturnal hemoglobinuria (PNH) chronically treated with the terminal complement inhibitor eculizumab. Ann Hematol. 2017 01 Apr 2017;96(4):589-96.
Bombardier C, Hazlewood GS, Akhavan P, Schieir O, Dooley A, Haraoui B, et al. Canadian rheumatology association recommendations for the pharmacological management of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs: Part II safety. J Rheumatol. 2012;39(8):1583-602.
Danzinger-Isakov L, Kumar D, AST Infectious Diseases Community of Practice, the AST Infectious Diseases Community of Practice. Guidelines for Vaccination of Solid Organ Transplant Candidates and Recipients. American Journal of Transplantation. 2009;9(s4):S258-62.
Eibl M.M., Wolf HM. Vaccination in patients with primary immune deficiency, secondary immune deficiency and autoimmunity with immune regulatory abnormalities. Immunotherapy. 2015 December 2015;7(12):1273-92.
Glück T, Müller-Ladner U. Vaccination in Patients with Chronic Rheumatic or Autoimmune Diseases. Clinical Infectious Diseases. 2008;46(9):1459-65.
Health Canada. Alert: Soliris (eculizumab) - Increased risk of hemolysis or low hemoglobin with serogroup B meningococcal vaccination. [Internet]. Ottawa: Health Canada; 2016-10-25 [updated 2016-10-25; cited 2016-10-25]. Available from: http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2016/60752a-eng.php.
Janssen M, Bruns A, Kuball J et al. Vaccine responses in adult hematopoietic stem cell transplant recipients: A comprehensive review. Cancers 2021, 13, 6140. https://doi.org/10.3390/cancers13236140
Kimberlin, MD, FAAP, David W., Long, MD, FAAP, Sarah S., Brady MT, Jackson MA. Red Book 2015: 2015 Report of the Committee on Infectious Diseases. 30th ed. Chicago; Elk Grove Village: American Academy of Pediatrics; 2015.
Leiding JW, MD, Holland SM, MD. Warts and all: Human papillomavirus in primary immunodeficiencies. Journal of Allergy and Clinical Immunology, The. 2012;130(5):1030-48.
Levin MJ, Song L, Fenton T, Nachman S, Patterson J, Walker R, et al. Shedding of live vaccine virus, comparative safety, and influenza-specific antibody responses after administration of live attenuated and inactivated trivalent influenza vaccines to HIV-infected children. Vaccine. 2008;26(33):4210-7.
L'Huillier A.G., Kumar D. Immunizations in solid organ and hematopoeitic stem cell transplant patients: A comprehensive review. Human Vaccines and Immunotherapeutics. 2015 01 Jan 2015;11(12):2852-63.
Ling J, Koren G. Challenges in vaccinating infants born to mothers taking immunoglobulin biologicals during pregnancy. Expert review of vaccines. 2016; 15(2):239-56.
Ljungman P, Cordonnier C, Einsele H et al. Vaccination of hematopoietic cell transplant recipients. Bone Marrow Transplant 2009;44:521-6.
Löbermann M, Boršo D, Hilgendorf I, Fritzsche C, Zettl UK, Reisinger EC. Immunization in the adult immunocompromised host. Autoimmunity Reviews. 2011; 2012; 11(3):212-8.
MacNeil J.R., Rubin L.G., Patton M., Ortega-Sanchez I.R., Martin SW. Recommendations for Use of Meningococcal Conjugate Vaccines in HIV-Infected Persons - Advisory Committee on Immunization Practices, 2016. MMWR. Morbidity and mortality weekly report. 2016 04 Nov 2016; 65(43):1189-94.
Lopez A., Mariette X., Bachelez H., Belot A., Bonnotte B., Hachulla E., et al. Vaccination recommendations for the adult immunosuppressed patient: A systematic review and comprehensive field synopsis. J Autoimmun. 2017 June 2017;80:10-27.
Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. [Internet]. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed June 26, 2019
Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected Children. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/oi_guidelines_pediatrics.pdf. Accessed June 26, 2019
Picard C, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, Conley ME, et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for primary immunodeficiency 2015. J Clin Immunol. 2015 Nov;35(8):696-726.
Pinto M.V., Bihari S., Snape MD. Immunisation of the immunocompromised child. J Infect. 2016 05 Jul 2016; 72:S13-22.
Public Health Agency of Canada. National Advisory Committee on Immunization (NACI) Statement: Recommended use of palivizumab to reduce complications of respiratory syncytial virus infection in infants June 01, 2022. Accessed February 17, 2023 at https://www.canada.ca/en/public-health/services/publications/vaccines-immunization/palivizumab-respiratory-syncitial-virus-infection-infants.html
Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, et al. 2013; IDSA clinical practice guideline for vaccination of the immunocompromised host. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2014;58(3):309-18.
Shearer W.T., Fleisher T.A., Buckley R.H., Ballas Z., Ballow M., Blaese R.M., et al. Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts. J Allergy Clin Immunol. 2014 April 2014;133(4):961-6.
Sobh A, MD, Bonilla, Francisco A.,MD, PhD. Vaccination in Primary Immunodeficiency Disorders. Journal of Allergy and Clinical Immunology: In Practice. 2016;4(6):1066-75.
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Date modified:: 2024-03-22

Immunization of immunocompromised persons: Canadian Immunization Guide

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On this page

Introduction and general principles

Non-live vaccines

Live attenuated vaccines

Immunoglobulins

Serologic testing and re-immunization

General principles

Family or medical history

Primary immunodeficiency

Predominantly antibody (B cell) deficiencies

Non-live vaccines

Live attenuated vaccines

Combined T and B cell immunodeficiencies (with or without associated /syndromic features) and Immune dysregulation

Non-live vaccines

Live attenuated vaccines

Phagocytic and neutrophil disorders

Non-live vaccines

Live attenuated vaccines

Complement deficiency

Non-live vaccines

Live attenuated vaccines

Defects of innate immunity

Non-live vaccines

Live attenuated vaccines

Acquired (secondary) immunodeficiency

Acquired complement deficiency

Malignant hematologic disorders

Non-live vaccines

Live attenuated vaccines

Non-hematologic malignant solid tumours

Non-live vaccines

Live attenuated vaccines

Hematopoietic stem cell transplantation (HSCT): autologous or allogeneic

Pre-HSCT immunization

Post-HSCT immunization

Non-live vaccines

Live attenuated vaccines

Solid organ transplantation

Pre-solid organ transplantation

Post-solid organ transplantation

Non-live vaccines

Live attenuated vaccines

Immunosuppressive therapy

Prior to immunosuppressive therapy

During or after immunosuppressive therapy

Non-live vaccines

Live attenuated vaccines

Infants exposed to immunosuppressive therapy in the womb

HIV infection

Non-live vaccines

Live attenuated vaccines

Close contacts

Immunocompromised travellers

Selected references

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