Rapidly acquired HIV-1 neutralization breadth in a rhesus V2 apex knockin mouse model after a single bolus immunization.
Year: 2026
Type: article
Abstract: 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.
Source: PubMed
Authors: Amrit Raj Ghosh, Rumi Habib, Nitesh Mishra, Ryan S Roark, Madhav Akauliya, Ali A Albowaidey, Joel D Allen, Khaled Amereh, Gabriel Avillion, Maria Bottermann, Bo Liang, Namit Chaudhary, Sean Callaghan, Jonathan Dye, Xuduo Li, Jordan R Ellis-Pugh, Rohan Roy Chowdhury, Nicole E James, Xiaotie Liu, Laura Maiorino, Paula M Villavicencio, Rebecca Nedellec, Prabhgun Oberoi, Kirsten J Sowers, Younghoon Park, Thavaleak Prum, Linette Rodriguez, Maria Ssozi, Jonathan L Torres, Agnes A Walsh, John E Warner, Stephanie R Weldon, Liling Xu, Kevin Wiehe, Max Crispin, Andrew B Ward, Usha Nair, Beatrice H Hahn, Dennis R Burton, Lawrence Shapiro, Peter D Kwong, Darrell J Irvine, Raiees Andrabi, George M Shaw, Facundo D Batista
Institutions: Ragon Institute of MGH, MIT and Harvard, Mass General Brigham, Massachusetts Institute of Technology, The Wistar Institute, University of Pennsylvania, Scripps Research Institute, Aaron Diamond AIDS Research Center, Columbia University, University of Southampton, Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research At MIT, Duke University, Duke Medical Center, Harvard University
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: Combining germline-targeting, B cell immunofocusing and Env-Ab coevolution strategies to induce HIV Envelope V2-apex broadly neutralizing antibodies, University of Pennsylvania - to develop a prophylactic vaccine against HIV, G5478737484, University of Pennsylvania - To develop a preventative HIV vaccine that can reach those at risk in low and middle income countries, The General Hospital Corporation d/b/a Massachusetts General Hospital - to advance HIV vaccine candidates by evaluation in fit for purpose experimental models, Combining germline-targeting, B cell immunofocusing and Env-Ab coevolution strategies to induce HIV Envelope V2-apex broadly neutralizing antibodies, G9000134098, Optimizing glycan shield coverage, germline B cell receptor binding and epitope diversity of V2-apex targeted HIV-1 Env immunogens, HIV-1 Q23.17 Env: Engineering a novel immunogen to elicit broadly neutralizing antibodies, Consortium for HIV/AIDS Vaccine Development
OpenAlex ID: W7128904074