As a chronically replicating virus, HIV has evolved extreme sequence variability and effective shielding of functionally constrained spike protein determinants by host-derived glycans1. Broadly neutralizing antibodies, although rare, can be isolated from people living with HIV, revealing conserved envelope glycoprotein (Env) sites as key targets for vaccine development2–4. One such target is the apex of the Env spike. Here we identify a vaccination strategy using heterologous HIV Env trimers covalently coupled to liposomes for multivalent display that resulted in the elicitation of cross-neutralizing HIV serum antibody responses in all trimer-liposome-immunized non-human primates. Critically, we isolated monoclonal antibodies from multiple macaques that cross-neutralize divergent HIV clinical isolates. High-resolution cryogenic electron microscopy structural analyses of monoclonal antibodies from four different macaques demonstrate that they target the Env trimer apex in a manner highly similar to that of the human-infection-elicited, apex-directed broadly neutralizing antibody PG9, representing a substantial advance in HIV vaccine development.
