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TitlePrecise targeting of HIV broadly neutralizing antibody precursors in humans.
Journal, issue, pagesScience, Page eadv5572, Year 2025
Publish dateMay 15, 2025
AuthorsTom G Caniels / Madhu Prabhakaran / Gabriel Ozorowski / Kellie J MacPhee / Weiwei Wu / Karlijn van der Straten / Sashank Agrawal / Ronald Derking / Emma I M M Reiss / Katrina Millard / Martina Turroja / Aimee Desrosiers / Jeffrey Bethony / Elissa Malkin / Marinus H Liesdek / Annelou van der Veen / Michelle Klouwens / Jonne L Snitselaar / Joey H Bouhuijs / Rhianna Bronson / Jalen Jean-Baptiste / Suprabhath Gajjala / Zahra Rikhtegaran Tehrani / Alison Benner / Mukundhan Ramaswami / Michael O Duff / Yung-Wen Liu / Alicia H Sato / Ju Yeong Kim / Isabel J L Baken / Catarina Mendes Silva / Tom P L Bijl / Jacqueline van Rijswijk / Judith A Burger / Albert Cupo / Anila Yasmeen / Swastik Phulera / Wen-Hsin Lee / Kipchoge N Randall / Shiyu Zhang / Martin M Corcoran / Isabel Regadas / Alex C Sullivan / David M Brown / Jennifer A Bohl / Kelli M Greene / Hongmei Gao / Nicole L Yates / Sheetal Sawant / Jan M Prins / Neeltje A Kootstra / Stephen M Kaminsky / Burc Barin / Farhad Rahaman / Margaret Meller / Vince Philiponis / Dagna S Laufer / Angela Lombardo / Lindsey Mwoga / Solmaz Shotorbani / Drienna Holman / Richard A Koup / Per Johan Klasse / Gunilla B Karlsson Hedestam / Georgia D Tomaras / Marit J van Gils / David C Montefiori / Adrian B McDermott / Ollivier Hyrien / John P Moore / Ian A Wilson / Andrew B Ward / David J Diemert / Godelieve J de Bree / Sarah F Andrews / Marina Caskey / Rogier W Sanders /
PubMed AbstractA protective HIV vaccine will need to induce broadly neutralizing antibodies (bnAbs) in humans, but priming rare bnAb precursor B cells has been challenging. In a double-blinded, placebo-controlled ...A protective HIV vaccine will need to induce broadly neutralizing antibodies (bnAbs) in humans, but priming rare bnAb precursor B cells has been challenging. In a double-blinded, placebo-controlled phase 1 human clinical trial, the recombinant, germline-targeting envelope glycoprotein (Env) trimer BG505 SOSIP.v4.1-GT1.1, adjuvanted with AS01, induced bnAb precursors of the VRC01-class at a high frequency in the majority of vaccine recipients. These bnAb precursors, that target the CD4 receptor binding site, had undergone somatic hypermutation characteristic of the VRC01-class. A subset of isolated VRC01-class monoclonal antibodies neutralized wild-type pseudoviruses and was structurally extremely similar to bnAb VRC01. These results further support germline-targeting approaches for human HIV vaccine design and demonstrate atomic-level manipulation of B cell responses with rational vaccine design.
External linksScience / PubMed:40373114
MethodsEM (single particle)
Resolution2.8 - 30.0 Å
Structure data

48283

9mi0

EMDB-48283, PDB-9mi0:
61-12A01 Fab in complex with HIV-1 GT1.1 v4.1 SOSIP Env trimer and RM20A3 Fab
Method: EM (single particle) / Resolution: 2.8 Å

48286

9mia

EMDB-48286, PDB-9mia:
206-3G08 Fab in complex with HIV-1 GT1.1 v4.1 SOSIP Env trimer and RM20A3 Fab
Method: EM (single particle) / Resolution: 2.8 Å

48287

9mib

EMDB-48287, PDB-9mib:
206-9C09 Fab in complex with HIV-1 GT1.1 v4.1 SOSIP Env trimer and RM20A3 Fab
Method: EM (single particle) / Resolution: 2.8 Å

48290

9mih

EMDB-48290, PDB-9mih:
273-4D01 Fab in complex with HIV-1 BG505 SOSIP Env trimer and RM20A3 Fab
Method: EM (single particle) / Resolution: 3.9 Å

48291

9mii

EMDB-48291, PDB-9mii:
253-7A03 Fab in complex with HIV-1 BG505 SOSIP Env trimer and RM20A3 Fab
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-70490: BG505 GT1.1 SOSIP in complex with gp41-base epitope polyclonal antibodies isolated from a participant in the IAVI C101 clinical trial
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70491: BG505 GT1.1 SOSIP in complex with V1V2V3 epitope polyclonal antibodies isolated from a participant in the IAVI C101 clinical trial
Method: EM (single particle) / Resolution: 30.0 Å

EMDB-70492: BG505 GT1.1 SOSIP in complex with C3V5 epitope polyclonal antibodies isolated from a participant in the IAVI C101 clinical trial
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-70493: BG505 GT1.1 SOSIP in complex with CD4bs epitope polyclonal antibodies isolated from a participant in the IAVI C101 clinical trial
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-70494: BG505 GT1.1 SOSIP in complex with gp41 glycan hole epitope polyclonal antibodies isolated from a participant in the IAVI C101 clinical trial
Method: EM (single particle) / Resolution: 27.0 Å

EMDB-70495: BG505 GT1.1 SOSIP in complex with gp41 fusion peptide epitope polyclonal antibodies isolated from a participant in the IAVI C101 clinical trial
Method: EM (single particle) / Resolution: 26.0 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • Human immunodeficiency virus
  • homo sapiens (human)
  • macaca mulatta (Rhesus monkey)
  • human immunodeficiency virus 1
KeywordsVIRAL PROTEIN / HIV-1 / SOSIP / germline targeting / VRC01 / clinical trial / human / precursor antibody

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