Year: 2024
Type: article
Abstract: Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to HIV and other pathogens. However, antibody-antigen recognition is typically dominated by heavy chain complementarity determining region 3 (HCDR3) interactions, and vaccine priming of HCDR3-dominant bnAbs by germline-targeting immunogens has not been demonstrated in humans or outbred animals. In this work, immunization with N332-GT5, an HIV envelope trimer designed to target precursors of the HCDR3-dominant bnAb BG18, primed bnAb-precursor B cells in eight of eight rhesus macaques to substantial frequencies and with diverse lineages in germinal center and memory B cells. We confirmed bnAb-mimicking, HCDR3-dominant, trimer-binding interactions with cryo-electron microscopy. Our results demonstrate proof of principle for HCDR3-dominant bnAb-precursor priming in outbred animals and suggest that N332-GT5 holds promise for the induction of similar responses in humans.
Source: Science
Authors: Jon M. Steichen, Ivy Phung, Eugenia Salcedo, Gabriel Ozorowski, Jordan R. Willis, Sabyasachi Baboo, Alessia Liguori, Christopher A. Cottrell, Jonathan L. Torres, Patrick J. Madden, Krystal M. Ma, Henry J. Sutton, Jeong Hyun Lee, Oleksandr Kalyuzhniy, Joel D. Allen, Oscar L. Rodriguez, Yumiko Adachi, Tina-Marie Mullen, Erik Georgeson, Michael Kubitz, Alison Burns, Shawn Barman, Rohini Mopuri, Amanda Metz, Tasha K. Altheide, Jolene K. Diedrich, Swati Saha, Kaitlyn Shields, Steven E. Schultze, Melissa L. Smith, Torben Schiffner, Dennis R. Burton, Corey T. Watson, Steven E. Bosinger, Max Crispin, John R. Yates, James C. Paulson, Andrew B. Ward, Devin Sok, Shane Crotty, William R. Schief
Institutions: Scripps Research Institute, La Jolla Institute for Immunology, University of California San Diego, University of Southampton, University of Louisville, Emory University, Emory National Primate Research Center, Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology, Moderna Therapeutics (United States)
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: G1066706594, G1987214103, International AIDS Vaccine Initiative - to demonstrate that an HIV ENV based immunogen(s) can be designed to elicit bnAbs in humans and has the potential to prevent HIV infection., International AIDS Vaccine Initiative - to develop and test vaccination strategies that are practical, deployable and have the potential to reduce HIV incidence, G3671455622, G4103933137, G6086104936, G690068069, G8103778937, G8371784529
OpenAlex ID: W4396977862