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TitleHIV Env trimers elicit NHP apex cross-neutralizing antibodies mimicking human bNAbs.
Journal, issue, pagesbioRxiv, Year 2025
Publish dateSep 22, 2025
AuthorsJavier Guenaga / Monika Adori / Shridhar Bale / Swastik Phulera / Ioannis Zygouras / Fabian-Alexander Schleich / Xaquin Castro Dopico / Sashank Agrawal / Miyo Ota / Richard Wilson / Jocelyn Cluff / Tamar Dzvelaia / Marco Mandolesi / Agnes 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
PubMed AbstractAs a chronically replicating virus, HIV has evolved extreme sequence variability and effective shielding of functionally constrained spike protein determinants by host-derived glycans. Broadly ...As a chronically replicating virus, HIV has evolved extreme sequence variability and effective shielding of functionally constrained spike protein determinants by host-derived glycans. Broadly neutralizing antibodies (bNAbs), though rare, can be isolated from people living with HIV, revealing conserved Env sites as key targets for vaccine development. One such target is the apex of the envelope glycoprotein (Env) spike. Here, we identified 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 immunized non-human primates (NHPs). Critically, we isolated a set of monoclonal antibodies (mAbs) that cross-neutralized multiple divergent HIV clinical isolates. High-resolution cryoEM structural analysis of mAbs from three different NHPs demonstrated that they targeted the Env trimer apex in a manner remarkably similar to that of the human infection-elicited, apex-directed bNAb PG9, representing a substantial advance in HIV vaccine development.
External linksbioRxiv / PubMed:41040226 / PubMed Central
MethodsEM (single particle)
Resolution20.0 - 30.0 Å
Structure data

EMDB-72735: HIV-1 Env Q23 NFL TD CC3+ in complex with NHP Q9 V2-apex polyclonal antibody Fabs isolated post-2 immunizations
Method: EM (single particle) / Resolution: 30.0 Å

EMDB-72736: HIV-1 Env Q23 NFL TD CC3+ in complex with NHP Q10 V2-apex polyclonal antibody Fabs isolated post-2 immunizations
Method: EM (single particle) / Resolution: 30.0 Å

EMDB-72737: HIV-1 Env Q23 NFL TD CC3+ in complex with NHP Q12 V2-apex polyclonal antibody Fabs isolated post-2 immunizations
Method: EM (single particle) / Resolution: 30.0 Å

EMDB-72738: HIV-1 Env 16055 NFL TD CC2+ in complex with pooled NHP Q8-Q9-Q12 V2-apex polyclonal antibody Fabs isolated post-4 immunizations
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-72739: HIV-1 Env BG505 NFL TD CC3+ in complex with pooled NHP Q8-Q9-Q12 V2-apex polyclonal antibody Fabs isolated post-4 immunizations
Method: EM (single particle) / Resolution: 20.0 Å

Source
  • Macaca mulatta (Rhesus monkey)
  • Human immunodeficiency virus 1

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