Vaccine elicitation of HIV-1 neutralizing antibodies against both V2 apex and fusion peptide in rhesus macaques
Year: 2026
Type: article
Abstract: Broadly neutralizing antibodies (bNAbs) targeting multiple sites of HIV-1 Env vulnerability can be induced by infection, but simultaneous elicitation of bNAbs against multiple epitopes has not been achieved by vaccination. In this study, we designed a dual-epitope vaccine targeting both the fusion peptide (FP) and the V2 apex and evaluated its capacity to induce bNAbs against both epitopes in rhesus macaques. This vaccine combined an FP conjugate with a cocktail of engineered Env trimers with enhanced V2 apex recognition and increased antigen retention in lymph nodes. Macaque immunization with the dual-epitope vaccine elicited >1,000-fold higher autologous tier 2-neutralizing titers than wild-type Env trimers and enhanced heterologous neutralization. Both FP- and V2 apex-monoclonal antibodies were isolated from immunized macaques and showed heterologous neutralization with genetic and structural signatures similar to well-characterized FP and V2 apex bNAbs. These results demonstrate proof of concept for simultaneous vaccine elicitation of neutralizing antibodies against multiple sites of Env vulnerability.
Source: Cell Reports
Authors: Hongying Duan, Joseph P. Nkolola, Shuishu Wang, Jayeshbhai Chaudhari, I-Ting Teng, Christy Lavine, Danealle K. Parchment, George S. Sellers, Krisha McKee, Sijy O’Dell, Misook Choe, Haijuan Du, Baoshan Zhang, Alejandro A. Espinosa Perez, Annika Rossler, Ninaad Lasrado, Andrea Biju, Jordan E. Becker, Robin Carroll, Audrey S. Carson, Amy R. Henry, Nicholas C. Morano, Madeeha Mughal, Reda Rawi, Ryan S. Roark, Chaim A. Schramm, Chen-Hsiang Shen, Sarah C. Smith, Tyler Stephens, Yaroslav Tsybovsky, David J. Van Wazer, Hua Wang, Yongping Yang, Lucy Rutten, Johannes P.M. Langedijk, Cheng Cheng, Lingshu Wang, Daniel C. Douek, Richard A. Koup, John R. Mascola, Lawrence Shapiro, Tongqing Zhou, Nicole A. Doria-Rose, Bette Korber, Michael S. Seaman, Theodore C. Pierson, Peter D. Kwong, Dan H. Barouch
Institutions: National Institutes of Health, National Institute of Allergy and Infectious Diseases, Vaccine Research Center, Beth Israel Deaconess Medical Center, Aaron Diamond AIDS Research Center, Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc. (United States), Janssen (Netherlands), New Mexico Consortium
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Awards: G1006578597, G312755629, G3189035245, G3984564396, Duke University - to facilitate the discovery and licensure of a safe, effective and practical HIV vaccine, or long-acting biologic intervention, to prevent the acqu..., G4572948833, Beth Israel Deaconess Medical Center Inc. - to test novel immunogen design strategies for HIV vaccine, G7019524645, G7380705155, G8491059191, G8567865963, G8962528392, G9000009240, G9000109445, G9000236556, G9000314919
OpenAlex ID: W7125929348