Significance Despite the high antigenic diversity of the HIV envelope trimer (Env), broadly neutralizing antibodies (bnAbs) have identified conserved regions that serve as targets for vaccine design. One of these regions is located at the apex of Env and is expressed fully only in the context of the correctly folded trimer. This work describes the isolation of bnAbs that target this region using a recombinant native-like Env trimer as an affinity reagent to sort specific antibody-producing cells. Characterization of these antibodies reveals a highly diverse antibody response against the trimer apex and provides molecular information that will be useful in the design of immunogens to elicit bnAbs to this region of Env.

Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex