Aspects of Vaccine Immunology

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Vaccines protect by inducing effector mechanisms (cells or. molecules) capable of rapidly controlling replicating patho- gens or inactivating their toxic components.  The predominant role of B cells in the efficacy of current vaccines should not overshadow the importance of T-cell responses: T cells are essential to the induction of high-affinity antibodies and immune memory, directly contribute to the protection conferred by current vaccines such as Bacille Calmette-Guérin (BCG), may play a more critical role than previously anticipated for specific diseases like pertussis, and will be the prime effectors against novel vaccine targets with predominant intracellular localization such as tuberculosis.

New methods have emerged allowing the assessment of a growing number of vaccine-associated immune parameters, including in humans. This development raises new questions about the optimal markers to assess and their correlation with vaccine-induced protection. The identification of mechanistic immune correlates or at least surrogates of vaccine efficacy is a major asset for the development of new vaccines or the optimization of immunization strategies using available vaccines. Thus, their determination generates a considerable amount of interest. During the last decade, the increased awareness of the complexity of the immune system and its determinants, including at the host genetic level, indicated that using system biology approaches to assess how various processes and networks interact in response to immunization could prove more illustrative than trying to isolate and characterize a few components of vaccine responses.

The induction of antigen-specific immune effectors (and/or of immune memory cells) by an immunization process does not imply that these antibodies, cells, or cytokines represent surrogates or even correlates of vaccine efficacy. This requires the formal demonstration that vaccine-mediated protection is dependent in a vaccinated person on the presence of a given marker such as an antibody titer or a number of antigen-specific cells above a given threshold.

B cells are essentially activated in the lymph nodes draining the injection site. Vaccine antigens reaching the sub-capsular sinus by free-fluid diffusion are taken up by specific sub-capsular sinus macrophages and translocate into the B-cell zone. The B cells equipped with surface B-cell receptors49 capable of binding to the vaccine antigens are activated and migrate to the interface between the B-cell (follicle) and the T-cell zones. There, B cells engage T cells and initiate their proliferation. The cumulative amount of co-stimulation signals received by B cells determines their fate. 50 Protein antigens (which are taken up and displayed as small peptides on the surface of APCs) activate Tfh cells. This induces a highly efficient B-cell differentiation pathway, through specific structures (germinal centers [GCs]) in which antigen-specific B cells proliferate and differentiate into antibody-secreting plasma cells or memory B cells. Polysaccharide antigens that fail to recruit Tfh cells into the response do not trigger GCs, such that they elicit only short-lived plasma cells resulting in weaker and less durable antibody responses with no immune memory.

The demonstration of the persistence of memory B cells long after vaccine antibodies have eventually disappeared, and of their brisk reactivation on antigen exposure, has direct consequences for immunization programs. First, it implies that an immunization schedule should never be started all over again but continued where interrupted, regardless of the duration of the interruption. Second, it implies that certain immunization schedules may not need to include booster doses, if the individual is exposed to regular natural boosters. It is intriguing to note, that in the absence of childhood boosters, up to 50% of adolescents or young adults primed against tetanus or hepatitis B in infancy might not raise anamnestic responses, suggesting that infant-induced vaccine memory may not last forever.

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Best Regards,

Mary Wilson,

Associate Managing Editor,

Medical Microbiology & Diagnosis

E-mail: microbiology@jpeerreview.com