Rational vaccine design

Despite extensive efforts, many infectious diseases, including AIDS, tuberculosis, and malaria, still lack effective and safe vaccines. Many noninfectious diseases, including cancer, autoimmune diseases, and allergy, also lack safe and effective vaccines. One reason for this lack is the absence of precise protective immune mechanism and immunological correlates of protection. These challenges can only be addressed with continuous productive research. Better rational vaccine design methods can only be developed after fundamental protective immunity mechanisms are better understood. 

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Whereas molecular design is a strategy applicable to the chemical level of epitope-paratope interactions, it cannot be used for optimizing the many cellular interactions required for achieving an immune response that leads to infectivity neutralization of a pathogen. As a result, the future development of vaccines will continue to rely more on the empirical testing of the protection afforded by candidate vaccine preparations than on the rational design of biomolecules defined in a reductionist manner by their chemical structure. 

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It may be possible to derive somewhat analogous information from observations of the phenotype of naturally occurring chemokine receptor polymorphisms in the context of HIV infection, both in vivo and in vitro. These kinds of investigation of the interaction between HIV and its coreceptors potentially contribute not only to an improved understanding of HIV pathogenesis, but also to the rational design of vaccine and drug interventions in clinical infection. 

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