HIV vaccine design based on in vivo evolution of quasispecies envelope proteins

Broadly neutralizing antibodies (bNAbs) against HIV remain a key goal for vaccine development. This work investigates whether sequential immunization with Env variants derived from HIV-infected individuals who developed bNAbs can guide B cell maturation toward breadth. Using phylogenetic analysis of viral quasispecies and antigenic profiling, we selected Env immunogens and tested DNA-plus-protein co-immunization strategies in rabbits. Results suggest that increasing Env sequence divergence and combining DNA with recombinant gp140 protein enhances neutralization responses compared to protein alone. These findings provide insight into antigenicity-immunogenicity relationships and inform rational design of HIV vaccines aimed at eliciting bNAbs.