Vaccination generates broadly cross-neutralizing antibodies to the HIV Env apex
- Javier Guenaga
- Monika Ádori
- Shridhar Bale
- Swastik Phulera
- Ioannis Zygouras
- Fabian-Alexander Schleich
- Xaquin Castro Dopico
- Sashank Agrawal
- Miyo Ota
- Richard Wilson
- Jocelyn Cluff
- Tamar Dzvelaia
- Marco Mandolesi
- Wen-Hsin Lee
- Agnes A. Walsh
- Mariane B. Melo
- Laurent Verkoczy
- Darrell J. Irvine
- Martin Corcoran
- Ian A. Wilson
- Diane Carnathan
- Guido Silvestri
- Andrew B. Ward
- Gabriel Ozorowski
- Gunilla B. Karlsson Hedestam
- Richard T. Wyatt
2026-04-29
As a chronically replicating virus, HIV has evolved extreme sequence variability and effective shielding of functionally constrained spike protein determinants by host-derived glycans 1 . Broadly neutralizing antibodies, although rare, can be isolated from people living with HIV, revealing conserved envelope glycoprotein (Env) sites as key targets for vaccine development 2–4 . 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.