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Smallpox and mpox vaccines: Canadian Immunization Guide

For health professionals

Notice

  • This chapter was updated in September 2024 based on a statement from the National Advisory Committee on Immunization (NACI): NACI interim guidance on the use of Imvamune® in the context of a routine immunization program published on May 24, 2024. There has been no new mpox vaccine guidance issued by NACI since the May publication.
  • The ACAM2000® vaccine has been authorized for use by Health Canada for active immunization against smallpox disease for persons 16 years of age and older determined to be at high risk for smallpox infection. For information on the use of this vaccine, refer to the product monograph in Health Canada's Drug Product Database.
Last partial content update: September 2024

The chapter was updated based on the following statements from the National Advisory Committee on Immunization (NACI): NACI interim guidance on the use of Imvamune® in the context of a routine immunization program published on May 24, 2024.

This information is captured in the table of updates.

Last complete chapter revision: January 2014

On this page

Please note: The Public Health Agency of Canada (PHAC) recognizes that not all people giving birth or breastfeeding will identify as women or mothers. The writing in this chapter uses a gender additive approach where the term “woman” is used alongside gender neutral language. This is intended to demonstrate a commitment to redress the historic exclusion of trans and non-binary people, whilst avoiding the risk of marginalizing or erasing the experience of women within the health care environment. However, in line with best practice, it is recognized that when discussing or caring for individuals in a one-on-one capacity, language and documentation should reflect the gender identity of the individual. Finally, PHAC acknowledges the dynamic nature of language. It is likely that language deemed to be suitable or affirming in one context may not translate across others, and over the coming years will likely change and evolve with respect to appropriate representations.

Key information

What

  • Vaccinia virus (causative agent of cowpox) is a member of the Orthopoxvirus genus and confers immunity against variola virus (causative agent of smallpox), monkeypox virus (causative agent of mpox) and other orthopoxviruses through cross-reactivity.
  • PHAC maintains several types of first- and second-generation vaccines (also known as Sma or live replicating vaccines) and third-generation vaccines (also known as SMV, or live-attenuated non-replicating vaccines).
  • Smallpox is a systemic viral illness with a characteristic rash that can have a 15 to 45% or higher mortality rate in an unimmunized population.
  • Naturally occurring smallpox disease was eradicated by 1977 through a worldwide vaccination program.
  • Remaining variola virus stocks are held under biosecurity in 2 World Health Organization (WHO) Collaborating Centre laboratories.
  • Since May 2022, cases of mpox have been reported and transmission has occurred in a number of countries where it was not previously reported, including Canada.

Who

  • Routine immunization of the general Canadian population with Sma vaccine is not recommended.
  • Personnel who work in research laboratory settings and who are at high risk of occupational exposure to replicating orthopoxviruses that pose a risk to human health are recommended for pre-exposure immunization with Sma or SMV.
  • SMV vaccination is recommended for individuals at high risk of mpox (pre-exposure immunization) as well as for individuals who have had high-risk exposure(s) to a probable or confirmed case of mpox, or within a setting where transmission is happening (post-exposure immunization).

How

  • Sma vaccines are administered by scarification into the epidermis, usually in the deltoid area of the non-dominant arm, by using the multiple-puncture technique with a bifurcated needle.
  • Contraindications to Sma vaccines are only applicable if the variola (smallpox) virus has not been introduced into the environment. In an outbreak situation, where a risk of infection exists, there are no absolute contraindications to immunization.
  • In a non-emergency setting, for people at higher risk of vaccinia complications, potential risks and benefits must be weighed, including vaccinia immunoglobulin (VIG) availability. SMV would be a better choice for these individuals, if available.
  • Should a smallpox case be suspected, immediate telephone communication with local or provincial/territorial public health officials is required; the PHAC should then be notified.
  • SMV is administered using a 2-dose schedule with a minimum interval of 28 days between doses.
  • Contraindications to SMV include hypersensitivity to this vaccine. Individuals with suspected severe hypersensitivity reactions (e.g., anaphylaxis) after receiving the first dose of the vaccine should consult an allergist.
  • SMV can be given concurrently (i.e., same day) or at any time before or after other live or non-live vaccines.
  • SMV vaccine supply is available to provinces and territories, upon request, by contacting PHAC's Centre for Emergency Response, Health Portfolio Operations Centre.
  • For outbreak management guidance involving immunization against mpox, the most recent National Advisory Committee on Immunization (NACI) statement should be consulted.

Why

  • To protect individuals at risk from monkeypox virus infection and other orthopoxvirus infections.
  • To prevent the re-emergence and spread of smallpox, a severe and frequently fatal disease that has been eradicated by vaccination.
  • A case of smallpox anywhere in the world constitutes a global health emergency.
  • Under the International Health Regulations, it is the responsibility of PHAC to notify the WHO if a case of smallpox is suspected.
  • For additional information, refer to NACI's Statement on Smallpox Vaccination (PDF format).

Epidemiology

Disease description

Infectious agent

Smallpox

Smallpox is a systemic viral disease caused by the Variola virus (major and minor), a species of the family Poxviridae, belonging to the genus Orthopoxvirus.

Refer to the Variola virus pathogen safety data sheet for additional information.

Mpox

Mpox is a systemic viral disease caused by the Monkeypox virus, a species of the family Poxviridae, belonging to the genus Orthopoxvirus. Monkeypox virus is subclassified into 2 clades: clade I (formerly known as Congo Basin or Central African clade) and clade II (formerly known as West African clade). Clade II has 2 subclades, clade IIa and clade IIb.

Refer to the Monkeypox virus pathogen safety data sheet for additional information.

Reservoir

Smallpox

The reservoir for variola virus is exclusively humans. There are no animal reservoirs of variola virus and the last human case occurred in 1978. Currently, the virus is maintained under biosecurity in 2 WHO Collaborating Centre laboratories.

Mpox

The reservoir for monkeypox virus is not fully understood, but main reservoirs are believed to be small mammals from endemic regions of West and Central Africa. Hosts include humans, squirrels, non-human primates, black-tailed prairie dogs, African brush-tailed porcupines, rats, and shrews.

Transmission

Smallpox

Smallpox is spread by droplets from the respiratory tract or by direct or indirect contact with the virus shed from skin lesions. Airborne spread is thought to be less frequent, but transmission over significant distances has been documented, including transmission through a hospital stairwell. In addition, the virus is stable in dried form for months and has been transmitted by fomites such as bed linen.

The incubation period for smallpox is from 7 to 19 days, typically 10 to 14 days to the onset of illness and 2 to 4 more days to the onset of the rash. Infectivity can occur at any time from the development of the rash to the disappearance of all scabs - approximately 3 weeks. Infectivity is highest early in the clinical disease.

Mpox

The monkeypox virus, both clade I and clade II, can spread through the following routes:

Human-to-human
  • By direct contact (including during sexual activity) with an infected person's body fluids, lesions on the skin or internal mucosal surfaces (e.g., mouth, throat, anogenital region) and
  • Via respiratory droplets
Fomites
  • By direct contact with virus-contaminated objects
Animal-to-human
  • From infected animals through a bite or scratch via direct contact with the infected animal's blood, body fluids, or lesions
  • By preparing or eating undercooked meat or using products from an infected animal

Mpox has a typical incubation period of 6 to 13 days from exposure, but can range from 5 to 21 days.

Risk factors

Smallpox

Canadians born in 1972 or later have not been routinely immunized against smallpox and are therefore considered susceptible to smallpox. Discontinuation of vaccination for travel was recommended by the WHO in 1980 and was no longer required by any country by 1982. There is currently no evidence to support routine smallpox immunization of the general Canadian population.

Personnel who work in research laboratory settings and who are at high risk of occupational exposure to replicating orthopoxviruses that pose a risk to human health are recommended for pre-exposure immunization with Sma or SMV.

Refer to Vaccination of specific populations for additional information.

Mpox

The following population groups are at higher risk of severe disease with mpox:

  • young children
  • pregnant women and pregnant individuals, and
  • immunocompromised individuals (e.g. individuals with uncontrolled human immunodeficiency virus (HIV) infection)

Since the 2022-2023 outbreak in Canada, the majority of infections have occurred as a result of sexual contact. In Canada, gay, bisexual, or other men who have sex with men (gbMSM) continue to be most affected by mpox. Sex workers, individuals working or volunteering at sex-on-premises venues and those who engage in sex tourism are also at high risk of mpox.

Vaccine eligibility based on increased risk for mpox should be informed by available clinical evidence and ongoing epidemiology. Risk factors may change over time and should be assessed by local and/or provincial/territorial public health.

Refer to Recommendations for use, Mpox for additional information.

Spectrum of clinical illness

Smallpox

Early symptoms of smallpox include the sudden onset of high fever, malaise, headache, fatigue, severe backache, and occasional abdominal pain and vomiting. After 2 to 4 days the fever subsides and there is a characteristic rash consisting of deep-seated lesions first appearing on the face and extremities, including the palms and soles, and subsequently on the trunk. The rash progresses through all the phases of macules, papules, vesicles, pustules and then crusted scabs that fall off 3 to 4 weeks after the appearance of the rash.

Mpox

Mpox disease is usually self-limiting and resolves within 14 to 28 days. The duration of communicability for monkeypox virus may be up to 2 to 4 weeks. People are considered infectious until all the lesions have scabbed, fallen off and been replaced with healed skin. Monkeypox virus clade II is associated with milder illness than clade I.

Refer to Mpox: For health professionals for additional information on the clinical manifestations of monkeypox virus infection.

Disease distribution

Incidence/prevalence

Global
Smallpox

The last known case of naturally occurring smallpox occurred in Somalia in 1977; 2 cases of smallpox occurred in England in 1978 as a result of a laboratory accident. In December 1979, the WHO officially declared that smallpox had been eradicated globally and in 1980 the World Health Assembly recommended all countries cease routine smallpox immunization programs.

Remaining variola virus stocks are held under biosecurity in 2 WHO Collaborating Centre laboratories in the United States (US) and Russia for research purposes. The occurrence of a single case of smallpox anywhere in the world constitutes a global health emergency.

Mpox

Mpox is endemic in Central and West Africa, but there have been cases and outbreaks in non-endemic countries due to international travel or the importation of infected animals from affected areas.

Clade IIb was responsible for the 2022 multi-country mpox outbreak and represented the first incidence of broader community transmission in a number of countries outside of certain regions of Africa. The international outbreak has primarily affected men who identify as gbMSM.

In 2024, a major mpox outbreak of clade I virus has been reported in the Democratic Republic of the Congo where almost half of cases have occurred among children under the age of 15 years.

National
Smallpox

Concerted vaccination campaigns were successful in eliminating endemic smallpox from Canada by 1946. Nova Scotia had a suspected case in 1949; with rigid quarantine, the disease did not spread. The final laboratory-confirmed case in Canada in 1962 involved an adolescent who returned to Toronto from Brazil.

Should a smallpox case be suspected, immediate telephone communication with local or provincial/territorial public health officials is required; the PHAC should then be notified.

Refer to Preparations for use in Canada, Vaccine availability for additional information.

Mpox

Canada has been one of the countries affected by the 2022 multi-country mpox outbreak. The 2022-23 mpox outbreak in Canada peaked around the end of June 2022 and was followed by a steady decrease in cases. Similar to other countries, gbMSM experienced a disproportionate burden of mpox in Canada (over 96% of all cases). Since December 31, 2023, Canada has continued to detect and report sporadic mpox cases, primarily among gbMSM, with sexual contact being the predominant mode of transmission.

Refer to Epidemiological summary report: 2022-23 mpox outbreak in Canada and Mpox (monkeypox) for additional information.

Preparations for use in Canada

Vaccinia virus (causative agent of cowpox) is a member of the Orthopoxvirus genus and confers immunity against variola virus (causative agent of smallpox), monkeypox virus (causative agent of mpox) and other orthopoxviruses through cross-reactivity. First- and second-generation vaccines are prepared from live, replicating vaccinia virus. Third-generation vaccine is prepared from live, non-replicating, modified vaccinia virus. PHAC maintains several types of first- and second-generation vaccines (also known as Sma or live replicating vaccines) and third-generation vaccines (also known as SMV, or live-attenuated non-replicating vaccines).

First-generation vaccines

  • SMALLPOX VACCINE (DRIED) (live vaccinia virus, bovine origin, smallpox vaccine) Sanofi Pasteur Limited. (Sma)
  • SMALLPOX VACCINE (LIQUID) (live vaccinia virus, smallpox vaccine) Aventis Pasteur Limited. (Sma)

Second-generation vaccine

  • ACAM2000® (live vaccinia virus, smallpox vaccine) Emergent Product Development Gaithersburg Inc. (Sma)*

* The ACAM2000® vaccine has been authorized for use by Health Canada for active immunization against smallpox disease for persons 16 years of age and older determined to be at high risk for smallpox infection. For information on the use of this vaccine, refer to the product monograph in Health Canada's drug product database.

Third-generation vaccine

  • IMVAMUNE® (live-attenuated, non-replicating, Modified Vaccinia Ankara-Bavarian Nordic® smallpox and mpox vaccine) Bavarian Nordic A/S. (SMV)

Imvamune® is authorized for use in Canada under the Extraordinary Use New Drug Submission (EUNDS) for active immunization against smallpox, mpox and related orthopoxvirus infection and disease in adults 18 years of age and older determined to be at high risk for exposure. Imvamune differs from first- and second-generation vaccines as it is a non-replicating vaccine virus in humans, meaning it is not able to produce more copies of itself.

Vaccine availability

Sma vaccines are not available for general use. For emergency situations (suspected or confirmed smallpox cases) contact PHAC's Centre for Emergency Response, Health Portfolio Operations Centre by telephone: 1-800-545-7661 or 613-952-7940 or e-mail: hpoc-cops@phac-aspc.gc.ca.

SMV vaccine supply is available to provinces and territories, upon request, by contacting PHAC's Centre for Emergency Response, Health Portfolio Operations Centre.

Vaccinia immunoglobulin

  • CNJ-016™ (vaccinia immunoglobulin [human]) Emergent BioSolutions Canada Inc. (VIG)

CNJ-016™ is a solution of gamma globulin from the serum of screened individuals with high titres of anti-vaccinia antibody. It is used to treat severe first- and second-generation vaccine-associated adverse events. VIG would be sent to the provinces/territories at the same time as first- and second-generation vaccine and related supplies if needed.

Refer to Contents of immunizing agents authorized for use in Canada in Part 1 for a list of vaccines and passive immunizing agents authorized for use in Canada and their contents.

Immunogenicity, efficacy and effectiveness

Smallpox

In the early 1970s before smallpox was eradicated, a retrospective study conducted in West Pakistan showed a mortality rate of 52% among those who had never been vaccinated, 1.7% among those who had been vaccinated within 10 years, and 11% among those who had been vaccinated 20 or more years earlier.

The specific mechanisms that result in immunity to smallpox following vaccination have not been well characterized. Studies conducted in the 1970s suggest that both antibody and cell-mediated immunity are stimulated by smallpox vaccination. A more recent study showed that more than 95% of primary vaccinees had detectable neutralizing antibody within 1 to 2 weeks after immunization and strong increases in vaccinia-specific CD8+ cytotoxic T lymphocytes and interferon-gamma-producing T cells.

Mpox

There is limited data on the effectiveness of SMV vaccination against monkeypox virus infection or mpox disease outside of outbreak settings. In outbreak situations, 1-dose effectiveness against infection has been estimated to range approximately from 35 to 85% and 2-dose effectiveness from approximately 65 to 85%. Protection against mpox was found to be somewhat lower in immunocompromised individuals, with 1- and 2-dose vaccine effectiveness being estimated at approximately 50 and 70%, respectively.

Immunological evidence has previously shown that vaccination with SMV generates an immune response by week two after immunization.

Recommendations for use

Smallpox

Given that naturally occurring smallpox has been eradicated worldwide and immunization with Sma vaccine is associated with the risk of significant morbidity and even mortality, the risk benefit analysis supports the recommendation to not routinely immunize the general Canadian population against smallpox. As a result, immunization with Sma vaccine is highly restricted.

Pre-exposure immunization with Sma or SMV is recommended for personnel who work in research laboratory settings and who are at high risk of occupational exposure to replicating orthopoxviruses that pose a risk to human health.

Refer to Vaccination of specific populations for additional information.

Mpox

Vaccination is recommended for individuals at high risk of mpox (pre-exposure immunization) as well as for individuals who have had high-risk exposure(s) to a probable or confirmed case of mpox, or within a setting where transmission is happening (post-exposure immunization).

Individuals with a previous or active monkeypox virus infection should not be offered SMV vaccination for pre- or post-exposure immunization. Healthcare professionals should use clinical judgement when considering vaccinating individuals who have an undocumented history of mpox infection.

Refer to Mpox: For health professionals for additional information on diagnosis of mpox and differential diagnosis of mpox rash.

High-risk criteria

Although there are limited data regarding SMV use among specific populations (e.g., immunocompromised due to disease or treatment; pregnancy or breastfeeding), these individuals are at higher risk of severe disease and should be offered SMV if vaccination is recommended based on high-risk criteria for pre- or post-exposure immunization.

Refer to Vaccination of specific populations for additional information.

Pre-exposure immunization

It is recommended that individuals at high risk of mpox should receive 2 doses of SMV administered at least 28 days (4 weeks) apart.

Individuals considered at high risk of mpox include:

  • Men who have sex with men (MSM) who meet one or more of the following criteria:
    • have more than one partner
    • are in a relationship where at least one of the partners has other sexual partners
    • have had a confirmed sexually transmitted infection acquired in the last year
    • have engaged in sexual contact in sex-on-premises venues
  • Sexual partners of individuals who meet the criteria above
  • Sex workers regardless of gender, sex assigned at birth, or sexual orientation
  • Staff or volunteers in sex-on-premises venues where workers may have contact with fomites potentially contaminated with mpox
  • Those who engage in sex tourism regardless of gender, sex assigned at birth, or sexual orientation
  • Individuals who anticipate experiencing any of the above scenarios

Pre-exposure immunization with Sma or SMV is recommended for personnel who work in research laboratory settings and who are at high risk of occupational exposure to replicating orthopoxviruses that pose a risk to human health.

Refer to Vaccination of specific populations for additional information.

Post-exposure immunization for high-risk exposure(s)

Post-exposure immunization with SMV is recommended to individuals if they have not received 2 doses of SMV and have had high-risk exposure(s):

  • to a probable or confirmed case of mpox OR
  • within a setting where transmission is happening

A post-exposure dose of SMV should be offered as soon as possible, preferably within 4 days of last exposure. However, it can be considered up to 14 days following last exposure. Regardless of ongoing exposure status, a second dose of SMV should be offered at least 28 days following the first dose if mpox did not develop.

Refer to Booster doses and re-immunization, Re-immunization following Sma vaccine for those recommended to receive SMV following a Sma vaccine.

Children at high risk of mpox (less than 18 years of age)

Pre-exposure immunization

Evidence is limited in pediatric populations less than 18 years of age, and the current SMV indication is for individuals 18 years of age and older. However, SMV may be considered for pre-exposure immunization for those less than 18 years of age who meet the high-risk criteria. If considering pre-exposure immunization, 2 doses of SMV are administered at least 28 days (4 weeks) apart.

Refer to Recommendations for use, Mpox for additional information.

Post-exposure immunization

For post-exposure immunization, off label use of SMV is recommended, with shared clinical decision making, for individuals less than 18 years of age who have had high-risk exposure(s). A post-exposure vaccine dose should be offered as soon as possible, preferably within 4 days of last exposure. However, it can be considered up to 14 days following last exposure. Regardless of ongoing exposure status, a second dose of SMV should be offered at least 28 days following the first dose, if mpox did not develop.

Refer to Recommendations for use, Mpox for additional information.

Catch-up schedules

Those who have started a primary series with SMV, in whom more than 28 days has passed without receipt of the second dose, should receive the second dose regardless of time since the first dose. However, individuals with history of a documented infection with mpox following the receipt of the initial vaccine dose need not be vaccinated.

Adults at high risk of mpox (18 years of age and older)

SMV is recommended for pre-exposure immunization of individuals at high risk of mpox and for post-exposure immunization for individuals who have had high-risk exposures.

Refer to Recommendations for use, Mpox, for additional information.

Catch-up schedules

Those who have started a primary series with SMV, in whom more than 28 days has passed without receipt of the second dose, should receive the second dose regardless of time since the first dose. However, individuals with history of a documented infection with monkeypox following the receipt of the initial vaccine dose need not be vaccinated.

Booster doses and re-immunization

Booster doses

Laboratory workers at high risk of occupational exposure

A booster dose or doses are recommended for personnel working in research laboratory settings where live variola virus or other replicating orthopoxviruses (including vaccinia virus and monkeypox virus) that pose a risk to human health may be stored, cultured or manipulated, and who remain at high risk of occupational risk of exposure.

Laboratory workers previously immunized with Sma vaccine

For these laboratory workers, who previously received a Sma vaccine, a booster dose of Sma should be given every 10 years.

Alternatively, for these laboratory workers who have previously received a Sma vaccine, if immunocompetent, a single booster dose of SMV may be offered (rather than a 2-dose primary series). This single booster dose of SMV should be given 2 years following the last dose of a Sma vaccine. At this time, there are no NACI recommendations on additional booster doses (i.e., more than one) using SMV.

Refer to Vaccination of specific populations, Immunocompromised persons for additional information for immunocompromised laboratory workers.

Laboratory workers previously immunized with third-generation vaccine

For these laboratory workers who received 2 doses of SMV it is recommended that an additional dose of SMV be offered 2 years following a primary series. At this time, there are no NACI recommendations on additional booster doses (i.e., more than 1) using SMV.

Individuals at high risk of mpox in community settings

At this time, there are no recommendations for additional doses of SMV (e.g., more than 2) for individuals at high risk in community settings, including immunocompromised populations. Evidence regarding the duration of protection following 2 doses of SMV for monkeypox virus infection is being monitored.

Re-immunization following Sma vaccine

Individuals at high risk of mpox or who have had high-risk exposures and have previously received a Sma vaccine, should be vaccinated with 2 doses of SMV administered at least 28 days (4 weeks) apart, regardless of immunocompromised status or age.

Refer to Recommendations for use, Mpox for additional information.

For laboratory workers who have previously received Sma vaccine(s), refer to Booster doses and re-immunization for additional information.

Outbreak control

Smallpox

A single case of smallpox is considered an outbreak.

In general terms, cases should be isolated immediately, preferably at home. If hospitalization is required, cases should be admitted to rooms under negative pressure equipped with high efficiency particulate air-filtration (HEPA) filters (airborne infection isolation rooms). Contacts and those living in the immediate vicinity of the identified case should be immunized immediately (ring vaccination) and placed under observation in quarantine.

Vaccination is indicated for face-to-face contacts (less than 6 feet or 2 meters), household contacts, personnel involved in the medical care, public health evaluation or transportation of confirmed or suspected smallpox cases, laboratory personnel involved in the collection or processing of clinical specimens from confirmed or suspected smallpox cases, and persons who have a high likelihood of exposure to infectious materials (e.g., those responsible for medical waste disposal, linen disposal or disinfection) of smallpox cases.

Vaccine can be given after exposure with beneficial effect as smallpox has a relatively long incubation period. Historical data collected during the smallpox eradication program using first-generation vaccine showed that vaccination within 2 to 3 days of exposure may protect against clinical disease, and if given within 4 to 5 days, may decrease the risk of death.

Mpox

Neither pre-exposure nor post-exposure immunization should be offered to individuals with a prior documented history of monkeypox virus infection or those who are symptomatic and meet the definition of a suspect, probable or confirmed mpox case.

Pre-exposure immunization

In the context of an active mpox outbreak, SMV should be offered to individuals at high risk of mpox.

Individuals considered moderately to severely immunocompromised and eligible for pre-exposure vaccination should be prioritized to receive two doses of SMV administered at the authorized interval (28 days between doses).

Refer to Recommendations for use, Mpox for additional information.

Post-exposure immunization

Post-exposure immunization using SMV should be offered to individuals with high-risk exposures to a probable or confirmed case of mpox, or within a setting where transmission is happening.

Refer to Recommendations for use, Mpox for additional information.

Individuals previously immunized with Sma vaccine

In the context of an active mpox outbreak, re-vaccination should be offered to individuals who have previously received a Sma vaccine and are at high risk of mpox or who have had high-risk exposures.

Refer to Booster doses and re-immunization, Re-immunization following Sma vaccine for additional information.

Limited vaccine supply during a mpox outbreak

In situations where there is ongoing mpox outbreak activity and limited vaccine supply, dose sparing strategies should be considered for pre-exposure immunization of immunocompetent individuals in order to expand coverage to a broader population. These strategies may include extending the interval between doses and intradermal fractional dose administration. Intradermal administration (ID) can be used among immunocompetent adults when given as a second dose following a first dose given subcutaneously (SC), provided dose sparing and safe administration practices are feasible. In situations where individuals received a first dose of SMV using an ID route, then the dose should be considered valid. Individuals who are less than 18 years of age, at risk of keloid scars, or moderately to severely immunocompromised should be offered SMV using the SC route of administration with a full dose only.

For additional details, refer to NACI's Rapid Response: Updated interim guidance on Imvamune® in the context of ongoing monkeypox outbreaks.

Vaccinia immunoglobulin

PHAC maintains a supply of VIG in the event of a smallpox emergency where use of first- and or second-generation vaccines are required. VIG is indicated to treat severe first- or second-generation vaccine-associated adverse events: eczema vaccinatum, progressive vaccinia, severe or recurrent generalized vaccinia, and extensive lesions resulting from accidental implantation (transfer of vaccinia virus from the primary vaccination site to other parts of the body). VIG is ineffective in the treatment of post-vaccinial encephalitis and has no role in the treatment or prevention of smallpox.

Vaccination of specific populations

Pregnancy and breastfeeding

Smallpox

In the non-emergency situation (prior to the occurrence of a case of smallpox), pregnant women and pregnant individuals should not receive Sma vaccine unless it is felt that the benefits of immunization greatly outweigh the risks and sufficient VIG is available to treat complications should they arise. Sma vaccine is not known to cause congenital malformations, but can very rarely lead to fetal vaccinia after primary immunization during pregnancy, resulting in stillbirth or neonatal death. However, in an emergency situation, if smallpox cases occurred and a real risk of infection existed, there would be no absolute contraindications to immunization.

Mpox

SMV should be offered to those who are pregnant or breastfeeding, if vaccination is recommended based on high-risk criteria. Pregnant women and pregnant individuals may particularly benefit from vaccination as these populations are at higher risk of severe disease with mpox.

Refer to Recommendations for use, Mpox for additional information.

Immunocompromised persons

Smallpox

In the non-emergency situation (prior to the occurrence of a case of smallpox), immunocompromised persons should not receive Sma vaccine unless it is felt that the benefits of immunization greatly outweigh the risks and sufficient VIG is available to treat complications should they arise. However, in an emergency situation, if smallpox cases occurred and a real risk of infection existed, there would be no absolute contraindications to immunization.

Mpox

Immunocompromised individuals are at higher risk of severe disease with mpox and should be offered SMV if vaccination is recommended based on high-risk criteria. When using SMV in immunocompromised individuals, 2 doses are recommended regardless of previous Sma vaccine history. These individuals should be offered SMV using the subcutaneous route of administration only.

Refer to Recommendations for use, Mpox for additional information.

Travellers

Mpox

Individuals at high risk of mpox and planning to travel internationally should consult with their healthcare provider on vaccination at least 4 to 6 weeks prior to travel, particularly those travelling to countries with ongoing mpox transmission. Individuals at high risk of mpox should receive 2 doses of SMV administered at least 28 days (4 weeks) apart. Individuals at high risk of mpox include those who engage in sex tourism (regardless of gender, sex assigned at birth, or sexual orientation). Healthcare providers should consider a traveler's responsibility to prevent the introduction and spread of mpox internationally in their recommendation to vaccinate.

Refer to Recommendations for use, Mpox for additional information.

Workers

Laboratory workers at high risk of occupational exposure

Smallpox and mpox

Pre-exposure immunization with Sma or SMV is recommended for personnel who work in research laboratory settings where live variola virus or other replicating orthopoxviruses (including vaccinia virus and monkeypox virus) that pose a risk to human health may be stored, cultured or manipulated and who are at high risk of occupational exposure.

If Sma is used, screening to identify and exclude individuals with contraindications to Sma immunization must be conducted. HIV testing should be considered. Adequate doses of VIG must be available prior to immunization in order to treat severe adverse events in case they arise.

If SMV is used, 2 doses should be given at least 28 days (4 weeks) apart.

A booster dose or doses are recommended for laboratory workers at high risk of occupational exposure.

Refer to Booster doses and re-immunization for additional information.

Other laboratory workers

Smallpox

Pre-exposure smallpox immunization of other laboratory workers is not recommended at the present time.

Mpox

Laboratory workers handling orthopoxviruses that do not put human health at risk, including those that cause disease only in animals or orthopoxviruses that are unable to replicate (including Modified Vaccinia Ankara) or laboratory workers who work outside of a research laboratory setting, including diagnostic laboratory or specimen transport workers, should not be offered pre-exposure immunization.

Healthcare workers and first responders

Smallpox

In the event of a suspect case of smallpox, vaccination of public health and health care personnel involved in the case investigation and clinical management is indicated. Once a case is confirmed, vaccination of public health staff and health care workers, as well as first responders such as police officers, firefighters, ambulance attendants, the military and others may also be indicated.

Healthcare workers

Mpox

Very few monkeypox infections related to occupational exposure among healthcare workers have been reported globally in non-endemic countries since January 2022.

SMV is not routinely recommended for healthcare workers, including those serving populations at high risk of mpox, with the exception of post-exposure immunization.

Refer to Recommendations for use, Mpox for additional information.

Staff or volunteers in sex-on-premises venues

Mpox

Staff or volunteers in sex-on-premises venues where workers may have contact with fomites potentially contaminated with mpox are considered at high risk of mpox. It is recommended that they should receive two doses of SMV administered at least 28 days (4 weeks) apart.

Refer to Recommendations for use, Mpox for additional information.

Serologic testing

Serologic testing is not recommended before or after receiving Sma vaccine.

Administration practices

First- and second-generation vaccines

Dose and route of administration

Sma vaccines are administered by scarification into the epidermis, usually in the deltoid area of the non-dominant arm, by using the multiple-puncture technique with a bifurcated needle, packaged with the vaccine and diluent (if applicable). According to the product labelling, 15 punctures are recommended for vaccination. A trace of blood should appear at the vaccination site after 15 to 20 seconds; if no trace of blood is visible, additional insertions should be made by using the same bifurcated needle without reinserting the needle into the vaccine vial. If alcohol is used to cleanse the skin before immunization, the skin must be allowed to dry thoroughly before the vaccine is administered, to prevent inactivation of the vaccine by alcohol.

Other methods of administration, such as multiple pressure method are possible in case bifurcated needles are not readily available. Refer to the product label for detailed instructions.

When vaccinia virus is inoculated into the epidermis, the virus induces an immune reaction that is termed "a take". There is often no visible reaction for the first few days. On day 3 to 4 a papule appears and progresses to a vesicle with surrounding erythema. Typically, one week or so after vaccination, the centre of the vesicle umbilicates and pustulates. After about 2 weeks, the pustule crusts and a dark brown or black scab forms. After 3 weeks, the scab detaches leaving a scar. The vaccination site should be inspected 6 to 8 days after vaccination to ensure that a take has occurred. If there is no evidence of papules or vesicles and erythema, the person should be vaccinated again.

Routine infection-control practices and appropriate vaccination site care should be used. Gloves should be worn by the vaccine provider when administering Sma vaccine due to the increased risk of autoinoculation from the use of a bifurcated needle. Each vaccinee and anyone caring for the vaccination site should wash their hands thoroughly after touching the site or handling bandages used to cover the site. Contaminated bandages and scabs should be placed in sealed plastic bags before disposal in the garbage. The vaccinee should avoid rubbing or scratching the site.

A sterile piece of porous bandage (e.g., gauze) should be used to loosely cover the vaccination site until the scab falls off in order to deter the vaccinee from touching the scab, to prevent inadvertent self-inoculation or inoculation of others, and to contain the scab so it is not lost. Preferably, a semi-permeable dressing should be placed over the gauze and not directly on the site; occlusive dressings should not be used. Dressings used to cover the site should be changed frequently to prevent accumulation of exudates and consequent maceration. Frequent dressing changes are particularly important for vaccinees who have close contact with children or people at high risk for vaccinia complications.

Concurrent administration with other vaccines

In non-emergency situations (i.e., non-outbreaks), Sma vaccines can be administered concurrently with any inactivated vaccine.

To avoid confusion in ascertaining which vaccine might have caused post-vaccination skin lesions or other adverse events, varicella (chickenpox) vaccine should not be administered concurrently with Sma vaccine; there must be an interval of at least 4 weeks between administration of varicella vaccine and Sma vaccine. Sma vaccine can be administered concurrently with other live parenteral vaccines; if not administered concurrently, there must be an interval of at least 4 weeks between Sma vaccine and other live parenteral vaccines.

Third-generation vaccine

Dose and route of administration

SMV is administered as 0.5 mL subcutaneously (SC) using a 2-dose schedule with a minimum interval of 28 days between doses.

In cases of limited vaccine supply, SMV can also be administered ID to immunocompetent adults using a fractional second dose (1/5th of SC dose). However, dose sparing strategies involving ID administration are not recommended in the context of routine immunization.

For information on the management of SMV administration errors, refer to Managing vaccine administration errors or deviations.

Concurrent administration with other vaccines

SMV can be administered concurrently (i.e., same day) or at any time before or after other live or non-live vaccines.

If concurrent administration with another vaccine is indicated, each vaccine should be administered in a different anatomic site (e.g., different limb) with separate injection equipment.

Vaccinia immunoglobulin

VIG should be given intravenously through a dedicated infusion line at a rate of 2 mL/min; VIG is compatible with sodium chloride 0.9%. Parenteral products should be inspected visually for particulate matter and discoloration prior to administration; it should not be used if the solution is turbid. The vial should not be shaken as it may cause foaming.

VIG should be administered at a dose of 6,000 units/kg as soon as symptoms appear and are judged to be due to a severe vaccinia-related complication. Two (2) exceptions to this are vaccinia keratitis and encephalitis. VIG should not be given for vaccinia keratitis due to the potential of increased corneal scarring, and should not be given for encephalitis due to lack of efficacy. For other VIG-treated complications, consideration may be given to repeat dosing, depending on the severity of the symptoms and response to treatment; however, clinical data on repeat doses are lacking. The administration of an additional dose of 9,000 units/kg may be considered in the event that the person does not respond to the initial 6,000 units/kg dose.

Post-vaccination counselling

All vaccine and VIG recipients should be instructed to seek medical care if they develop signs or symptoms of a serious adverse event or an allergic reaction following immunization.

Refer to Vaccine administration practices in Part 1 for additional information on pre- and post-vaccination counseling.

Storage requirements

First-generation vaccines

Smallpox Vaccine (Dried) should be stored in a refrigerator at +2°C to +8°C and reconstituted before use.

Smallpox Vaccine (Liquid) is frozen for long-term storage. Once thawed, the vaccine should be maintained between +2°C and +8°C. Open vaccine vials should be used within 24 hours.

Third-generation vaccine

SMV should be stored frozen at -20°C ± 5°C or -50°C ± 10°C or -80°C ± 10°C. The shelf-life at each of these storage temperatures is dependent on a number of factors, including time since date of manufacture. After thawing, the vaccine should be used immediately or can be stored at +2°C to +8°C for up to 2 months prior to use. Do not refreeze a vial once it has been thawed. Store in the original package to protect from light.

SMV is formulated as a single dose vial and does not contain preservatives. In cases of limited vaccine supply, when used for multiple doses, the vial must be discarded after 6 hours from first puncture in order to reduce the risk of contamination of the vial or infection.

Refer to Imvamune: Storage temperatures, shelf life, shipment and supportive temperature excursion information for additional specific information.

Refer to Storage and handling of immunizing agents in Part 1 for additional general information.

Safety and adverse events

Common adverse events occur in 1% to less than 10% of vaccinees. Very common adverse events occur in 10% or more of vaccinees.

Uncommon adverse events occur in 0.1% to less than 1% of vaccinees. Rare and very rare adverse events occur, respectively, in 0.01% to less than 0.1% and less than 0.01% of vaccinees.

Refer to Vaccine Safety and pharmacovigilance Part 2 for additional general information.

First- and second-generation vaccines

Common adverse events

In a UK study of 200 health care workers, 142 (71%) of vaccinees reported pain at the injection site, of which 25% considered it to be moderate or severe; 32 vaccinees (16%) recorded a temperature of greater than 37.7°C, two of which exceeded 39°C. Other, mainly minor, adverse events were common; local itching was reported in 72%, erythema at the injection site in 27%, axillary pain or lymphadenopathy in 38%, malaise or influenza-like symptoms in 40% and headache in 23%. The incidences of minor adverse events were lower in re-vaccinees, compared with primary vaccine recipients. The study used a single dose of the Swiss Serum Institute (SSI) vaccine, containing the Elstree/Lister strain of vaccinia virus.

Less common and serious or severe adverse events

Inadvertent inoculation

Inadvertent inoculation is the transfer of the virus from the site of immunization to other body sites or other persons resulting in vaccinia lesions. The most susceptible areas are the eye, mouth, nose, face and genitalia. Children are most susceptible to inadvertent inoculation. Inadvertent inoculation is the most common (significant) adverse reaction, with rates approaching 600 cases per million doses administered. Most ensuing lesions heal spontaneously. There are case reports of secondary and tertiary vaccinia arising in sexual contacts of a person recently vaccinated; these cases were severe enough to require VIG to manage vaccinia-related complications. When a secondary case of vaccinia is diagnosed, contract tracing is indicated to ascertain whether there are additional secondary or tertiary cases.

Generalized vaccinia

Generalized vaccinia may occur within a week after vaccination. Lesions appear on unimmunized skin and are thought to arise from viremia. Lesions are similar to those associated with the vaccination site but are usually smaller and evolve to scarring more rapidly, often within a week. In healthy individuals, this is a benign complication of primary vaccination that needs to be differentiated from progressive vaccinia. Individuals with underlying and unsuspected immunosuppressive illnesses may develop a serious reaction.

Progressive vaccinia (Vaccinia Necrosum)

Progressive vaccinia is a very rare, severe, complication following immunization with first- or second-generation vaccines. It often occurs because of an immune defect, especially T cell deficiencies. It is characterized by progressive necrosis at the site of immunization and, in the presence of viremia, leads to implants in distant skin sites and multiple organs. Progression is slow, persistent and resistant to treatment. In those with profound T cell defects, it is nearly always fatal.

Eczema vaccinatum

Eczema vaccinatum occurs in vaccinees or their unvaccinated contacts with active or healed eczema lesions or other exfoliative skin conditions. Vaccinial skin lesions appear on skin that is currently or was previously affected by eczema. Usually the illness is mild and self-limited, but it can be severe and fatal.

Vaccinia keratitis

Vaccinia keratitis can threaten eyesight through corneal abrasions, ulcerations and subsequent corneal clouding. If this occurs, consultation with an ophthalmologist is strongly recommended. VIG is contraindicated because of the potential of increased corneal scarring.

Post-vaccinial encephalitis

Post-vaccinial encephalitis is a rare but serious complication that can develop 7 to 14 days after vaccination. There are no known predictors of susceptibility, but the incidence is somewhat higher among infants less than 1 year of age. Approximately, 25% of cases with encephalitis develop permanent sequelae (both motor and/or intellectual impairment) and up to 35% die. VIG is not recommended due to lack of efficacy.

Acute myopericarditis

During a first-generation vaccination program for US military personnel which started in 2002, a previously unreported adverse event, acute myopericarditis, was recognized. Most of the affected vaccinees experienced chest pain and returned to normal activities within 7 to 10 days, and all recovered. It is unclear whether these events were adverse outcomes following first-generation vaccination. The first-generation vaccine (Dryvax, Wyeth Laboratories) containing the New York City Board of Health strain of vaccinia was used in this program.

VIG is available to treat certain first- and second-generation vaccine-associated adverse events. Refer to Preparations for use in Canada, Vaccinia immunoglobulin for additional information.

Third-generation vaccine

Common adverse events

Most adverse events develop within a few days after receiving the vaccine.

The most common local adverse events following SMV immunization are pain, erythema, induration and swelling at the site of injection. The most common systemic adverse reactions observed after SC vaccination with SMV are fatigue, headache, myalgia, and nausea. Most of these reactions are mild to moderate intensity and resolve within the first seven days following vaccination.

Less common and serious or severe adverse events

In clinical trials, cardiac adverse events of special interest (AESI) were reported to occur in 1.4% (91/6,640) of SMV recipients, 0.2% (3/1,206) of placebo recipients who were Sma vaccine-naïve and 2.1% (16/762) of SMV recipients who were Sma vaccine-experienced. Among the cardiac AESIs reported, 6 cases were considered to be causally related to SMV vaccination. The events reported included tachycardia, electrocardiogram T wave inversion, abnormal electrocardiogram, electrocardiogram ST segment elevation, abnormal electrocardiogram T wave, and palpitations. None of the 6 events considered vaccine-related were considered serious.

In post-marketing safety studies, serious adverse events were rarely reported. Specifically, there was no signal for increased risk of myocarditis or anaphylaxis following vaccination, and no new or unexpected safety concerns were identified. In Canada, data from the Canadian National Vaccine Safety Network (CANVAS) showed that SMV was well tolerated. Health events interfering with work/school or requiring medical assessment were less common among vaccinated individuals versus unvaccinated controls. No participants were hospitalized within seven or 30-days following vaccination. Furthermore, no cases of severe neurological disease, skin disease, or myocarditis were identified.

No trends have been identified which suggest the occurrence of any particular unexpected adverse reaction or classes of adverse reactions following vaccination. To date, myocarditis has not been determined to be causally associated with SMV but monitoring is ongoing.

Guidance on reporting adverse events following immunization (AEFI)

To ensure the ongoing safety of vaccines in Canada, reporting of AEFIs by vaccine providers and other clinicians is critical.

Vaccine providers are asked to report, through local public health officials, any serious or unexpected adverse event thought to be temporally related to vaccination with SMV or Sma including any case of secondary or tertiary vaccinia. An unexpected AEFI is an event that is not listed in available product information but may be due to the immunization, or a change in the frequency of a known AEFI.

Refer to Adverse events following immunization in Part 2 and the User guide to completion and submission of the AEFI reports for additional information about AEFI reporting.

The Brighton case definitions are also available.

Contraindications and precautions

First- and second-generation vaccines

Contraindications to Sma vaccines are only applicable if the variola (smallpox) virus has not been introduced into the environment. In an outbreak situation, if smallpox cases are occurring and a risk of infection exists for an individual, there are no absolute contraindications to immunization.

The product monograph lists the following contraindications in a non-emergency setting. For people at higher risk of vaccinia complications, potential risks and benefits must be weighed, including VIG availability. SMV would be a better choice for these individuals, if available.

Persons less than 18 years of age

Sma vaccines are contraindicated for children and adolescents because they are more likely to suffer from adverse reactions and cause inadvertent self-reinoculation and inoculation of others.

Hypersensitivity or anaphylaxis

Sma vaccines are contraindicated in people with a history of anaphylaxis after previous administration of the vaccine and in persons with proven immediate or anaphylactic hypersensitivity to any component of the vaccine or its container. For Sma vaccines, potential allergens include: streptomycin, neomycin and latex in the stopper of the vial.

Refer to Contents of immunizing agents authorized for use in Canada in Part 1 for lists of all vaccines and passive immunizing agents authorized for use in Canada and their contents.

Immunodeficiency or immunocompromised

Sma vaccines are contraindicated for people who are immunocompromised. Refer to Immunization of immunocompromised persons in Part 3 for additional information.

Atopic dermatitis and other widespread skin disorders

Diffuse vaccinia virus infection can occur in the presence of acute atopic dermatitis and other widespread exfoliative skin disorders.

Pregnancy and breastfeeding

Sma vaccine is generally contraindicated in pregnant women and pregnant individuals in non-emergency situations although it is not known to cause congenital malformations. It can very rarely lead to fetal vaccinia after primary immunization during pregnancy, resulting in stillbirth or neonatal death. Women and individuals of childbearing age should be asked before vaccination if they are pregnant or intend to become pregnant during the next 4 weeks. If a woman or individual becomes pregnant within 4 weeks after Sma vaccination, the healthcare provider should offer enhanced monitoring of the pregnancy.

Breastfeeding women and breastfeeding individuals should not receive the Sma vaccine in non-emergency situations. The close physical contact that occurs during breastfeeding increases the chance of inadvertent inoculation of the baby. It is not known whether vaccine virus or antibodies are excreted in human milk.

A breastfeeding woman or breastfeeding individual should only be immunized if they have been exposed to smallpox and SMV is not available; in that case breastfeeding and other close contact should be delayed until after the vaccination scab has separated from the vaccination site.

Heart disease and cardiac risk factors

Sma is contraindicated in people with known underlying heart disease (with or without symptoms), or who have three or more known major cardiac risk factors (i.e., hypertension, diabetes, hypercholesterolemia, heart disease at age 50 years or younger in a first-degree relative, and smoking). A risk assessment needs to be done in an emergency situation such as exposure to a case of smallpox.

The product monograph lists the following precautions:

Ocular or periorbital disease

Persons with inflammatory eye disease may be at increased risk for inadvertent inoculation as a result of touching or rubbing the eye. Therefore, deferring vaccination is prudent for persons with inflammatory eye diseases requiring steroid treatment until the condition resolves and the course of therapy is complete.

Close contacts

Generally, Sma vaccine should not be administered to household contacts of an immunocompromised person in a non-emergency situation. If vaccination is required in an outbreak situation, precautions should be taken for unvaccinated household and other close contacts. Vaccinees with household and other close contacts with active eczema or a history of eczema or other exfoliative skin conditions, immunocompromising conditions, or with close contact with infants or pregnant women, should take special precautions in order to prevent viral transfer to these contacts. Such precaution can include isolation of the vaccinee from their higher risk household contacts until the vaccine scab falls off.

Third-generation vaccine

Contraindications to SMV include hypersensitivity to this vaccine. Individuals with suspected severe hypersensitivity reactions (e.g., anaphylaxis) after receiving the first dose of the vaccine should consult an allergist. There is evidence that some individuals with immediate allergic reactions to vaccines in general (although less data are available for SMV) can safely receive a subsequent dose of the same vaccine with low risk of a systemic reaction under the supervision of an allergist. Individuals with confirmed or suspected hypersensitivity to the potential allergens contained in the vaccine components (egg, tromethamine, or antibiotics) can receive the vaccine without expert consultation; prolonged observation (30 minutes) may be considered.

Data on SMV are limited in pregnant women and pregnant individuals, those who are breastfeeding or those less than 18 years of age. SMV should be offered to these populations if vaccination is recommended based on high-risk criteria.

Refer to Recommendations for use, Mpox for additional information.

Vaccinia immunoglobulin

The most common adverse events related to VIG are headache, nausea, rigors and dizziness.

Relative contraindications to VIG include:

  • a history of systemic allergic reactions to human immunoglobulin products
  • isolated vaccinia keratitis due to the potential of increased corneal scarring
  • selective immunoglobulin A deficiency with antibodies against IgA and a history of IgA hypersensitivity (because VIG contains trace amounts of IgA)

It is not known whether VIG can cause fetal harm when given to a pregnant woman or a pregnant individual. However, immunoglobulins have been widely used during pregnancy for many years without any apparent negative reproductive effects. Counselling based on an individual risk benefit assessment is indicated. VIG should not be withheld if a pregnant woman or pregnant individual experiences a condition for which VIG is needed.

Refer to Contraindications and precautions in Part 2 for additional general information.

Other considerations

Drug interactions

There is some evidence for tuberculin skin test (TST) suppression following the administration of live, attenuated virus vaccines; a TST can be done on the same day as immunization or delayed until 4 weeks after administering a Sma vaccine.

Definitions

MSM

Man or Two-Spirit identifying individual who has sex with another person who identifies as a man, including but not limited to individuals who self-identify as trans-gender, cis-gender, Two-Spirit, gender-queer, intersex, and non-binary.

Pre-exposure immunization

Vaccine dose(s) to prevent disease administered prior to potential exposure to an infectious agent; also sometimes referred to as pre-exposure vaccination or prophylaxis.

Post-exposure immunization

Vaccine dose(s) to prevent disease administered shortly following a known or presumed exposure to an infectious agent, or a setting where transmission is happening, and before the development of any symptoms; also sometimes referred to as post-exposure vaccination or prophylaxis.

Chapter revision process

This chapter was updated to reflect guidance based on current evidence and NACI's expert opinion on the use of Imvamune® in the context of a routine immunization program.

Acknowledgements

The chapter was updated based on the NACI statement: NACI Interim guidance on the use of Imvamune® in the context of a routine immunization program prepared by N Forbes, K Klein, J Montroy, M Salvadori, K Gusic, and X Yiao, V Dubey, R Harrison, MC Tunis, on behalf of NACI. The chapter was prepared by L Coward, O Baclic and reviewed by N Forbes, M Salvadori, A Coady and K Klein.

The CIG gratefully acknowledges the contribution of: C Jensen and N Haddad.

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