Principles of combination vaccines: Canadian Immunization Guide

For health professionals

Last complete chapter revision (see Table of Updates): March 2018

What is a Combination Vaccine?

There are three types of vaccine preparations based on how many and what types of immunizing antigens are contained in the vaccine:

vaccines containing one immunizing antigen against one disease (for example, hepatitis A vaccine)
vaccines containing immunizing antigens against more than one serogroup or serotype of the same disease (for example, quadrivalent meningococcal vaccine, pneumococcal vaccines)
vaccines containing immunizing antigens against more than one vaccine preventable disease (for example, measles-mumps-rubella vaccine)

The nomenclature to describe these types of vaccines is used inconsistently. The term combination vaccine is often used to refer to a single vaccine that includes antigens for the prevention of more than one vaccine preventable disease, and is used in that context in this chapter. The term combined vaccines may also be used to describe the prescribed mixture of two separate vaccines in a single vial prior to administration, or vaccines that are separately manufactured but combined by the manufacturer into one product during the final packaging stages.

There are many combination vaccine products available. Diphtheria, tetanus and pertussis vaccines have been available as combination products for more than 30 years, and infants in Canada have been vaccinated against diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae type b with a combination vaccine containing all five antigens since 1996. In recent years, additional combination vaccine products have become available and new combination vaccines have been added to the routine immunization schedule. Refer to Contents of Immunizing Agents Available for Use in Canada for a list of vaccines and their contents, brand names and abbreviations. For details on specific combination vaccines, refer to the vaccine-specific chapters in Part 4.

General Principles of Combination Vaccines

Combination vaccines are rigorously evaluated and only those combinations that have been demonstrated to be safe and efficacious are authorized for use in Canada.
In general, combination vaccines are preferred over separate injections of single component vaccines to minimize the number of injections required.
Combination vaccines should fit the recommended immunization schedule, be easily stored, and be easy to administer.
Vaccines that are intended for separate administration should never be combined by vaccine providers unless mixing is explicitly specified in the product leaflet or product monograph. The safety, immunogenicity, and effectiveness of unlicensed combinations are unknown.

Efficacy of Combination Vaccines

The efficacy of each component in a combination vaccine is compared with established parameters of protection before the combination vaccine is authorized for use in Canada. Antibody responses to specific antigens in combination products may be either stronger or weaker than responses to separately administered single antigens; however, these differences are not considered to be clinically significant.

Safety of Combination Vaccines

The combination products available in Canada have excellent safety records. The safety of a new combination product is rigorously evaluated and compared against the safety of single antigen products or existing combination vaccines prior to authorization for use in Canada. There may be differences in minor adverse events associated with combination vaccines when compared to single component vaccines, but these differences are not considered to be clinically significant. In case of an adverse event following immunization, determining which component of a combination vaccine caused the adverse event may be more challenging than in single component vaccines.

With the refinement of vaccine development and production, and the use of combination vaccines, children today are exposed to fewer vaccine antigens than in the past and are protected against more infections.

Refer to Adverse events following immunization in Part 2 for additional information.

Benefits of Combination Vaccines

The benefits of combination vaccines include:

Improved adherence to immunization schedules because of a reduction in the number of immunization visits and injections required, leading to improved vaccine coverage rates.
Facilitation of uptake of a new vaccine when combined with an older vaccine (for example, measles-mumps-rubella-varicella vaccine).
Increased opportunity for administration of catch-up or booster doses of vaccine (for example, timely vaccination of children who are behind in their routine immunization schedule).
Reduced risk of injury to vaccine providers related to multiple injections of separate vaccines.
Reduced time required for an immunization visit when one injection rather than multiple injections are given.
Reduced vaccine administration, shipping, handling, wastage and storage costs.
Reduced costs for extra immunization visits.
Reduced stress for vaccine recipients and vaccine providers related to multiple injections of separate vaccines.

Refer to Benefits of Immunization in Part 1 for additional information.

Complexities of Combination Vaccines

Complexities associated with combination vaccines include:

Combination products may be more expensive than separate vaccines; however, combination vaccines may be more cost effective if the costs of extra injections, health care provider time, and additional handling and storage are taken into consideration.
It can be difficult to determine which component of a combination vaccine is responsible for an allergic reaction or other adverse event following immunization.
The use of a combination product may result in administration of extra, unneeded doses of antigens (for example, a booster dose of pertussis-containing vaccine may also provide extra, unneeded doses of tetanus toxoid and diphtheria toxoid).

Adverse effects of repeated immunization with the following vaccines have not been demonstrated, regardless of possible prior receipt of the vaccine: combined measles-mumps-rubella with or without varicella; inactivated polio; Haemophilus influenzae type b; meningococcal; hepatitis A; hepatitis B; univalent varicella; Tdap and influenza vaccines.

For other antigens, there may be an increased risk of an adverse event when the extra antigen dose is administered prior to the recommended interval if it had not been part of a combination product. Before administering a combination vaccine with an extra, unneeded antigen or antigens, the benefits and risks of administering the combination vaccine should be considered and discussed with the vaccine recipient or parent. Using combination vaccines containing extra, unneeded antigens may be justified when:

the extra antigen is not contraindicated; and
products that contain only the needed antigens are not readily available; and
the benefits to the vaccine recipient outweigh the potential risk of adverse events associated with the extra antigen dose.

Selected References

Centers for Disease Control and Prevention. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2011;60(2):1-61.
Happe LE, Lunacsek OE, Kruzikas DT et al. Impact of a pentavalent combination vaccine on immunization timeliness in a state Medicaid population. Pediatr Infect Dis J 2009;28:98-101.
Kalies H, Grote V, Verstraeten T et al. The use of combination vaccines has improved timeliness of vaccination in children. Pediatr Infect Dis J 2006;25:507-12.
Marshall GS, Happe LE, Lunacsek OE et al. Use of combination vaccines is associated with improved coverage rates. Pediatr Infect Dis J 2007;26:496-500.
Scheifele DW. Combining vaccines: does it make sense and does it work? Accessed July 2015 at: http://www.onehealth.ca/r_alberta_nwt/video_conferences/R080312B-HOb.pdf

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Date modified:: 2021-09-23

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