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How Vaccines Work ?Immunology of Vaccination
Dr. Vikram Gupta
How Vaccines Work?
Dr. Vikram GuptaAssistant Professor,
Department of Community Medicine,Dayanand Medical College & Hospital, Ludhiana
Agenda
• 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 rules1. Count the number of vaccine doses that are necessary for
protection – separately for each antigen2. 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 administration is different
Young Age Immunization
1. Young age limits antibody responses to most vaccine antigens: Why ?
• Maternal antibodies inhibits antibodies responses but not T-Cell response
• Limitation of B cell responses2. Induction of B memory cells is not limited3. Antibody responses elicited in early life are
short lasting
Strategies• So what are the 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 interval
depends on disease epidemiology.
Acknowledgement
• 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….
