Precise targeting of HIV broadly neutralizing antibody precursors in humans.

TitlePrecise targeting of HIV broadly neutralizing antibody precursors in humans.
Publication TypeJournal Article
Year of Publication2025
AuthorsCaniels TG, Prabhakaran M, Ozorowski G, MacPhee KJ, Wu W, van der Straten K, Agrawal S, Derking R, Reiss EIMM, Millard K, Turroja M, Desrosiers A, Bethony J, Malkin E, Liesdek MH, van der Veen A, Klouwens M, Snitselaar JL, Bouhuijs JH, Bronson R, Jean-Baptiste J, Gajjala S, Tehrani ZRikhtegara, Benner A, Ramaswami M, Duff MO, Liu Y-W, Sato AH, Kim JYeong, Baken IJL, Silva CMendes, Bijl TPL, van Rijswijk J, Burger JA, Cupo A, Yasmeen A, Phulera S, Lee W-H, Randall KN, Zhang S, Corcoran MM, Regadas I, Sullivan AC, Brown DM, Bohl JA, Greene KM, Gao H, Yates NL, Sawant S, Prins JM, Kootstra NA, Kaminsky SM, Barin B, Rahaman F, Meller M, Philiponis V, Laufer DS, Lombardo A, Mwoga L, Shotorbani S, Holman D, Koup RA, Klasse PJohan, Hedestam GBKarlsson, Tomaras GD, van Gils MJ, Montefiori DC, McDermott AB, Hyrien O, Moore JP, Wilson IA, Ward AB, Diemert DJ, de Bree GJ, Andrews SF, Caskey M, Sanders RW
JournalScience
Volume389
Issue6759
Paginationeadv5572
Date Published2025 Jul 31
ISSN1095-9203
KeywordsAdjuvants, Immunologic, AIDS Vaccines, Antibodies, Monoclonal, B-Lymphocytes, Broadly Neutralizing Antibodies, CD4 Antigens, Double-Blind Method, env Gene Products, Human Immunodeficiency Virus, HIV Antibodies, HIV Infections, HIV-1, Humans, Somatic Hypermutation, Immunoglobulin
Abstract

A protective HIV vaccine will need to induce broadly neutralizing antibodies (bnAbs) in humans, but priming rare bnAb precursor B cells has been challenging. In a double-blinded, placebo-controlled phase 1 human clinical trial, the recombinant, germline-targeting envelope glycoprotein (Env) trimer BG505 SOSIP.v4.1-GT1.1, adjuvanted with AS01B, induced bnAb precursors of the VRC01-class at a high frequency in the majority of vaccine recipients. These bnAb precursors, which target the CD4 receptor binding site, had undergone somatic hypermutation characteristic of the VRC01-class. A subset of isolated VRC01-class monoclonal antibodies neutralized wild-type pseudoviruses and was structurally extremely similar to bnAb VRC01. These results further support germline-targeting approaches for human HIV vaccine design and demonstrate atomic-level manipulation of B cell responses with rational vaccine design.

DOI10.1126/science.adv5572
Alternate JournalScience
PubMed ID40373114
PubMed Central IDPMC12313413
Grant ListINV-008352 / GATES / Gates Foundation / United States
INV-007371 / GATES / Gates Foundation / United States
INV-036842 / GATES / Gates Foundation / United States
INV-008017 / GATES / Gates Foundation / United States
INV-002916 / GATES / Gates Foundation / United States
INV-029691 / GATES / Gates Foundation / United States
INV-007368 / GATES / Gates Foundation / United States
INV-032929 / GATES / Gates Foundation / United States
INV-002202 / GATES / Gates Foundation / United States
P01 AI110657 / AI / NIAID NIH HHS / United States
INV-008818 / GATES / Gates Foundation / United States
R01 AI036082 / AI / NIAID NIH HHS / United States
INV-007375 / GATES / Gates Foundation / United States

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