Rapidly acquired HIV-1 neutralization breadth in a rhesus V2 apex knockin mouse model after a single bolus immunization.
Current immunization strategies to elicit broadly neutralizing antibodies (bnAbs) against HIV-1 generally propose complex, multiboost regimens. In rhesus macaques, simian-human immunodeficiency virus (SHIV) infection rapidly drives the development of some bnAb classes sharing structural similarities with those in humans. Here, we generated a knockin (KI) mouse model with B cells bearing the unmutated common ancestor of a V2 apex-targeted bnAb lineage, V033-a. A single immunization with a germline-targeting native-like trimer, Q23-APEX-GT1, recapitulated the ontogeny of the mature rhesus bnAb in KI mice, including rare, disfavored somatic mutations. Resulting antibodies exhibited potent neutralization against a broad panel of heterologous HIV-1 strains. Boosting with Env escape mutant trimers further improved breadth and potency, and cryo-electron microscopy analysis revealed the structural basis for heterologous neutralization breadth. Nonhuman primate and mouse models combined with structure can serve as a platform for identifying and validating immunogens that streamline HIV vaccination regimens.
Authors
- Rebecca Nedellec
- John E. Warner (ORCID: https://orcid.org/0009-0001-1043-1643)
- Usha Nair (ORCID: https://orcid.org/0000-0002-1927-6889)
- Maria Bottermann (ORCID: https://orcid.org/0000-0002-8178-100X)
- Bo Liang
- Madhav Akauliya (ORCID: https://orcid.org/0009-0009-0325-6080)
- Pranav Oberoi
- Linette Rodriguez
- Ali Albowaidey
- Rumi Habib (ORCID: https://orcid.org/0000-0002-2812-8263)
- Paula Maldonado Villavicencio (ORCID: https://orcid.org/0009-0008-2321-9669)
- Jonathan Dye (ORCID: https://orcid.org/0000-0003-2801-8053)
- Laura Maiorino (ORCID: https://orcid.org/0000-0001-8217-1337)
- Xiao Liu (ORCID: https://orcid.org/0000-0003-0588-5699)
- D. J. Irvine
- Stephanie R. Weldon (ORCID: https://orcid.org/0000-0001-5384-9946)
- D Burton
- Ryan S. Roark (ORCID: https://orcid.org/0000-0003-0586-103X)
- Sean Callaghan (ORCID: https://orcid.org/0000-0003-2966-994X)
- Namit Chaudhary (ORCID: https://orcid.org/0000-0002-2115-7731)
- Rohan Roy Chowdhury (ORCID: https://orcid.org/0000-0003-3586-571X)
- Amrit Raj Ghosh
- Nicole E. James (ORCID: https://orcid.org/0000-0003-4342-4770)
- Thavaleak Prum (ORCID: https://orcid.org/0009-0004-6973-5053)
- Jordan Renae Ellis-Pugh
- Kirsten J. Sowers
- Agnes A. Walsh
- Maria Ssozi
- Е.В. Голосов
- Kevin Wiehe
- Joel D. Allen
- Nitesh Mishra
- Raiees andrabi
- Xuduo Li
- Younghoon Park (ORCID: https://orcid.org/0009-0003-5069-504X)
- Gabriel Avillion
- Jonathan L Torres
- Max Crispin
- Facundo D Batista
- Andrew B Ward
- Beatrice H Hahn
- George M Shaw
- Liling Xu
- Lawrence Shapiro
- Peter D Kwong
Institutions
- The Wistar Institute (US)
- Scripps Research Institute (US)
- International AIDS Vaccine Initiative (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- Aaron Diamond AIDS Research Center (US)
- Duke University (US)
- Ragon Institute of MGH, MIT and Harvard (US)
- University of Southampton (GB)
- Massachusetts Institute of Technology (US)
- Columbia University (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- PubMed
- Published
- 2026-02-13
- DOI
- https://doi.org/10.1126/sciimmunol.adz5064
- Citations
- 1
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 27.20