Immunogen design to focus the B-cell repertoire.
PURPOSE OF REVIEW: This review aims to bring together recent developments relevant to the design of HIV-1 envelope glycoprotein-based immunogens to elicit broadly neutralizing antibodies (bNAbs). RECENT FINDINGS: The combined use of structural biology and deep sequencing of antigen-specific B-cell lineages has allowed cross-sectional and longitudinal views of antibody evolution towards broad and potent neutralization of HIV-1. Recent advances in molecular modelling allied with protein and glycoprotein engineering have fuelled the design of new-generation viral envelope glycoproteins (Env)-based antigens. SUMMARY: Although proof-of-principle for vaccine elicitation of bNAbs to HIV-1 is still lacking, many of the conceptual hurdles are being addressed.