Canadian Immunization Guide
Seventh Edition - 2006
Canadian Immunization Guide 2006
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Part 1
General Guidelines
Principles of Combination
Vaccines
Combination vaccine products are already
available for many immunizations conducted in Canada. Diphtheria,
tetanus and polio vaccines have been available as a combination
product for over 30 years. Since 1996, all infants in Canada have
been vaccinated against diphtheria, tetanus, pertussis, polio
and Haemophilus influenzae type b (DTaP-IPV-Hib )
with a single, pentavalent vaccine.
Over the past few years, the number of
combination vaccine products has grown considerably, and this
trend will continue with more vaccines being introduced to the
routine immunization schedule for children and adults. As new products are recommended, it is
important for the immunization provider to feel comfortable with
the principles of combination vaccines. This chapter serves as a general
overview of these principles. For details on specific combination
vaccines, please refer to the individual chapters in this Guide.
What is a combination
vaccine?
Combination vaccines are developed to
protect against more than one infection. Polyvalent vaccines
against multiple strains or serotypes of the same infectious
agent are not considered to be combination vaccines. The term
"combined vaccines" may also be used to describe the
mixture of two separate vaccines in a single vial prior to
administration or vaccines that are separately manufactured but
combined into one product during the final packaging
stages.
General principles of combination
vaccines
- Combination vaccines are rigorously
evaluated before approval for use in Canada. Only those
combinations that are known to be safe and efficacious are
recommended for routine use. For an overview of vaccine safety,
including that of specific combination products, please refer to
the chapter on Vaccine
Safety.
- Ideal combination vaccines are as safe
and effective as each of their single component
counterparts.
- Combination vaccines should fit the
currently recommended schedule, be easily stored and easy to
administer.
- Combination vaccines facilitate
adherence to recommended immunization schedules by reducing the
number of immunization visits required as well as the number of
injections a person receives.
- Combination products can potentially
decrease the amount of adjuvants and preservatives when compared
with multiple, single-antigen products.
- Health care providers should never
combine products that are intended for separate
administration.
Efficacy of combination
vaccines
- The efficacy of each component in a
combination vaccine is compared with established parameters of
protection before approval.
- Antibody responses to specific antigens
in combination products may be either stronger or weaker than
those to separately administered single antigens.
- The impact of any observed changes in
antibody titres is assessed against the known human protective
levels of antibodies or other indicators of efficacy.
- Combination vaccines approved to date
have an efficacy and safety record similar to that of
single-component vaccines.
- The addition of Hib to the combination
vaccine with tetanus, diphtheria, acellular pertussis and polio
did not result in diminished immune responses to the tetanus,
diphtheria, acellular pertussis and polio components. The
response to the Hib antigens was somewhat reduced; however, a
significant impact on clinical efficacy when the vaccine was
administered according to the Canadian immunization schedule was
not demonstrated through post-marketing studies.
Safety of combination
vaccines
- The currently available combination
products in Canada have had excellent safety records.
- Ideal combination vaccines should have
fewer adverse reactions or, at the very least, no more than if
administering single-antigen products separately.
- The safety of each new combination
product is rigorously evaluated prior to approval and compared
against the safety of single-antigen products or existing
combination vaccines.
- New combination vaccines help to further
our knowledge regarding co-administration of antigens as
combination vaccines, as they are all well evaluated before
approval.
- The vaccine provider may face questions
from parents about their feelings that multiple combination
vaccines can weaken the immune system.
- With the refinement of vaccine
development and production over past decades, children today are
exposed to far fewer vaccine antigens than in the past, even
though they are immunized against more infections with more
combination vaccines.
- Children are naturally exposed to
multiple antigens on a routine basis. They respond well to these persistent
exposures with no untoward effects on their immune
system.
- If multiple antigens posed a problem for
the immune system, we would find that infants vaccinated with
combination products had less protection against the infection
than those vaccinated with single products. This has not been
found.
Complexities of combination
vaccines
- The efficacy and safety of each
component in a combination must be evaluated separately and in
its combined form, thereby increasing the complexity of
pre-approval clinical trials.
- Clinically important interference
between each component of a combination vaccine must be ruled
out. Antibody responses to individual antigens in combination
products may be diminished. Given that antibody responses are
only a surrogate for clinical efficacy, assessing or estimating
the clinical relevance of this is complex. In the development of
new combination products, acceptable endpoints and immunization
goals should be clearly defined.
- The measurement of potency and antigen
content of combination products is more complex and difficult.
- Even a single, transient problem in the
production of an individual component of a combination product
could lead to a significant shortage in vaccine supply for
multiple diseases.
- In the context of combination products,
the effects of adjuvants can be difficult to assess.
- It can be difficult to determine which
component is responsible for an allergic or other adverse
event.
- There are usually increased costs
associated with combination product procurement.
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