A. Ghosh, Rumi Habib, Nitesh Mishra, Ryan S Roark, Madhav Akauliya, Ali A. Albowaidey, J. D. Allen, Khaled Amereh, Gabriel Avillion, Maria Bottermann, Bo Liang, Namit Chaudhary, Sean Callaghan, Jonathan Dye, Xuduo Li, J. R. Ellis-Pugh, Rohan Roy Chowdhury, Nicole E James, Xiaotie Liu, L. Maiorino, P. Villavicencio, R. Nedellec, Prabhgun Oberoi, Kirsten J Sowers, Younghoon Park, Thavaleak Prum, Linette Rodriguez, Maria Ssozi, J. Torres, Agnes A. Walsh, John E Warner, S. Weldon, Liling Xu, K. Wiehe, Max Crispin, Andrew B. Ward, Usha Nair, B. H. Hahn, Dennis R. Burton, Lawrence Shapiro, Peter D. Kwong, Darrell J. Irvine, Raiees Andrabi, G. Shaw, Facundo D. Batista
2026.2.13Science Immunology
tlooto Summary
Non-human primate and mouse models combined with structure can serve as a platform for identifying and validating immunogens that streamline HIV-vaccination regimens.
Abstract
Current immunization strategies to elicit broadly neutralizing antibodies (bnAbs) against HIV-1 generally propose complex, multi-boost 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 (UCA) 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 viruses. Boosting with Env escape mutant trimers further improved breadth and potency, and cryo-EM analysis revealed the structural basis for heterologous neutralization breadth. Non-human primate and mouse models combined with structure can serve as a platform for identifying and validating immunogens that streamline HIV-vaccination regimens.
Citation format
GHOSH, A., et al. Rapidly acquired HIV-1 neutralization breadth in a macaquized v2 apex mouse model after a single bolus immunization. Science Immunology, 2026, 11(116): eadz5064-eadz5064.