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Guiding antibody evolution via programmable antigen environments
Antibodies, soluble forms of B cell receptors, attain increasing affinity for encountered antigens by alternating between somatic mutation and competitive selection in a cyclic fashion, a phenomenon known as affinity maturation. But this Darwinian process becomes ineffective in facing highly mutable complex pathogens, such as HIV, which have evolved various tactics to escape and divert immune responses. I will describe the challenges in inducing broadly neutralizing antibodies by vaccination, present an in silico model of affinity maturation driven by multiple antigens with complex epitopes, and discuss immunization strategies that can potentially focus antibody response on the targeted viral vulnerability which test favorably by in vivo experiment.