Figure 1.

Hypothetical priming immunogen composition for an HIV vaccine designed to induce bNAbs. The primary immunogenic composition is engineered to activate a diverse repertoire of B cells, which preferentially differentiate into memory B cells capable of re-entering germinal centres in response to secondary and tertiary booster immunization rather than inducing short-lived plasma cells and plasma cell-committed memory B cells. Such a composition would contain antigen in moderate abundance and with a multivalent, repetitive structure in order to crosslink B cell antigen receptors (i.e. surface immunoglobulin) with a range of affinities for this primary immunogen. The immunogen structure would be engineered to preferentially engage the unmutated common ancestors of bNAbs rather than narrowly neutralizing antibodies. The adjuvant in the formulation would effectively upregulate MHC class II and costimulatory molecules on antigen-presenting cells and foster the differentiation of Tfh without strongly inducing CD4 T-cell-polarizing cytokines.