Purpose of review
It has been demonstrated that extensive virus diversification and antibody co-evolution is necessary to give rise to broadly neutralizing antibodies (bnAbs) targeting the envelope protein (Env) of HIV-1. Here we discuss recent progress of vaccine design approaches aiming on strategies to initiate and guide B cell development towards this outcome, as well as their evaluation in mouse models engineered to express human antibodies.
Recent findings
Several specially tailored transgenic mouse strains have been developed in order to test the concept of engaging and guiding B cell development by sequential immunizations. Currently available models display pre-rearranged or non-rearranged germline or mature VDJH and VJL loci of CD4-binding-site- (VRC01, 3BNC60) and high-mannose-patch-specific (PGT121) bnAbs, or even the complete human V(D)J segments. Data generated in these knock-in mouse models elegantly prove the feasibility of the concept when using a carefully selected panel of engineered envelope proteins.
Summary
Recent studies in knock-in transgenic mouse models provide a proof-of-concept that germline B cell receptor targeting followed by sequential immunization can engage the respective naïve precursor B cells and guide B cell receptor development towards broadly neutralizing reactivity.