An HIV-1 antibody from an elite neutralizer implicates the fusion peptide as a site of vulnerability.

The induction of broadly HIV-1 neutralizing antibodies (bNAbs) by vaccination is challenging, but understanding how a subset of HIV-infected individuals (elite neutralizers) develops bNAbs may guide immunization strategies. Here, we describe the isolation and characterization of the bNAb ACS202 from an elite neutralizer that recognizes a new, trimer-specific and cleavage-dependent epitope at the gp120-gp41 interface, involving the glycan N88 and the gp41 fusion peptide. In addition, an Env trimer, AMC011 SOSIP.v4.2, based on early virus isolates from the same elite neutralizer, was constructed and its structure by cryo-EM at 6.2 Å resolution reveals a closed, pre-fusion conformation similar to previously solved BG505 Env trimers. The availability of native-like Env trimers and a bNAb from the same elite neutralizer provides the opportunity to design vaccination strategies aimed at generating similar bnAbs against a key functional site on HIV-1