Common HIV-1 escape patterns drive the maturation of V2-Apex broadly neutralizing antibodies. Homo sapiens

Designing a vaccine capable of eliciting broadly neutralizing antibodies (bnAbs) to HIV requires a better understanding of bnAbs maturation pathways as it occurs in interplay with the HIV envelope glycoprotein evolution during natural infection. Here we describe the second example of a developmental pathway for bnAbs targeting the HIV-1 V2-Apex in co-evolution with the autologous virus. Similar to other Abs of this class, the PCT64 lineage bears a moderate 25aa-long anionic CDRH3, projecting as tight -hairpin. We found that glycan heterogeneity at N160 was critical for the PCT64 germline activation, and that the Env escape pathway driving the bnAbs maturation is very similar to another donor with V2-apex targeting bnAbs, suggesting that these Env evolution patterns could be exploited for immunogen design. Comparison of these two donors provides important insight regarding the maturation pathways of bnAbs and critical information for vaccine design.