How Vaccines Dr.

Vikram Gupta
Work ? Immunology
of Vaccination
How Vaccines
Work?

Dr. Vikram
Gupta
Assistant
Professor, Department of Community
Medicine, Dayanand Medical College &
 Agend
a

• How do vaccines work?

Which are the main effectors of vaccine
responses?

• How Vaccine responses are elicited,

supported, maintained and/or reactivated
by vaccine antigens
Innate and Adaptive
immunity
First steps after
immunization
• So in case of deltoid injection draining
lymphnodes will be axillary group and in case
of quadriceps it will be inguinal group of
lymph nodes.
 Non-live
•
vaccines
No microbial replication at site of injection so vaccine-
induced activation of dendritic cells (DC’s) is limited, both
in time and space.
• Immunogenicity of non live vaccines is
• limited Site and route of administration is
• important
Simultaneous administration of several distinct vaccines
• may take place without immune interference.
DCs are numerous in the well-vascularized muscles, which
• is the preferred route of injection for most vaccines.
Dendritic cells are in highest number in the skin – this
allows a marked reduction (e.g. 10 fold) of the antigen dose
in intradermal immunization, an advantage that is applied to
the prevention of rabies in many countries.
 Live
vaccines
• Replicate, disseminate and activate dendritic
cells at multiple sites launching multiple foci
of T and B cell activation
• Immunogenicity of live vaccines is higher
• Site and route of administration is unimportant
• Simultaneous administration- Immune
interference may occur unless they are given
on the same day or if the routes of
administration are different (eg OPV with other
live vaccines
• These plasma cells migrate towards the red pulp of the spleen
where they survive for a few weeks / months, secreting low
levels of low affinity IgM, IgG or IgA antibodies.

• As PS (polysachharide) antigens do not induce germinal

centres, bona fide memory B cells are not elicited.
Consequently, subsequent re-exposure to the same PS
results
into a repeat primary response that follows the same kinetics
in previously vaccinated as in naïve individuals.
• Revaccination with certain bacterial PS - of which group C
meningococcus is a prototype - may even induce lower
antibody responses than the first immunization, a phenomenon
referred to as hyporesponsiveness and whose molecular and
cellular basis is not yet fully understood.
 What affects primary
vaccine antibody
responses?
• Vaccine types: Live vs inactivated , Protein vs
PS, Adjuvants
• Antigen dose: Higher the dose-higher
primary response.
• Vaccine Schedule: 4 weeks minimum
interval between primary doses avoids
interference
• Genetic, Environmental factors , Age
What controls persistence of Vaccine
antibody responses?
• Nature of vaccine- only live vaccine
induces long lasting antibody resonse,
shortest response by PS antigens
• Vaccine schedules- Interval between
primary doses, Interval before boosting
• Age at immunization -shorter at two
extremes of age
• Disease conditions
 Hallmarks of B cell memory
responses?
• Memory B cells do not protect
• Reactivation occurs in response to natural boosters
by pathogens or booster immunization
• On reactivation antibodies appear in blood very
rapidly (4-7 days) as proliferation and differentiation
occurs without requiring development of Germinal
• center
Antibodies are of markedly higher affinity ( they can
be only induced when sufficient time has passed
after priming)
 Immune Memory – implications
for immunization programs
• Immunization schedule should never be started “all
over again” regardless of duration of interruption
• Regular boosters are not required to maintain
immune memory during low risk periods (Travellers)
• Certain immunization schedules may not need boosters
if exposure provides regular natural boosters
• Booster may not be needed where reactivation of
immune memory by offending pathogen is sufficiently
rapid and effective to interrupt microbial invasion
(Hep
B)
 Vaccine catch-up
1. rules
Count the number of vaccine doses that are necessary
for protection – separately for each antigen
2. Substract doses received = missing doses !
3. Do not give more doses than an unimmunized child
would receive !
4. Choose the optimal intervals between missing doses

• Baseline rule : 0 – 1 – 6 months (i.e. 6 month interval)

• All missing vaccines may be given on the same day – at distant
sites (>2.5cm) !
• All missing vaccines may be given at any interval (days,
weeks)
…
• Except 2 live viral vaccines : 0 or 4 weeks (…)
• Since vaccination induces immunological memory
the vaccination schedule need not be started all
over again. Only the remaining doses need to be
given.
• For live viral vaccines, they should be either given
on the same day or after 4 weeks to prevent
immunologic interference. Exceptions are
1.BCG and measles/ MMR should not be given on
the same day as measles depresses CMI that
interferes with uptake of BCG.
2.OPV may be given at any interval from any
live vaccine because the route of
 Young Age
Immunization
1. Young age limits antibody responses to
most vaccine antigens: Why ?
• Maternal antibodies inhibits
antibodies responses but not T-Cell
• response
LimitationofofBBmemory
2. Induction cell responses
cells is not limited
3. Antibody responses elicited in early life
are short lasting
 Strategi
• So what are thees
strategies to overcome
these shortcomings during early infancy?
• We give more doses or give vaccine at
later age?
• It is not possible to give vaccine
late as most of these diseases
occur at early age.
• We give more doses of vaccines in
comparison to adults and older children.
• Age for starting vaccination and time
 Acknowledgem
ent
• This presentation is based on Science of
Vaccinology Module of IAP and Advac Course
.
• International Vaccine Conference was held,
by IAP at New Delhi in November 2008 and
slides were part of resource material.
Reference:
1. Siegrist CA : Vaccine Immunology .
In:Vaccines.5th edition .Elsevier.2007 ,2,20-34.
THANX
….