Precise targeting of HIV broadly neutralizing antibody precursors in humans.
Science (New York, N.Y.)
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 AS01 B , 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.
Authors and publication
Caniels 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, Rikhtegaran Tehrani Z, Benner A, Ramaswami M, Duff MO, Liu YW, Sato AH, Kim JY, Baken IJL, Mendes Silva C, Bijl TPL, van Rijswijk J, Burger JA, Cupo A, Yasmeen A, Phulera S, Lee WH, 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 PJ, Karlsson Hedestam GB, 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.
- Journal
- Science (New York, N.Y.)
- Publication year
- 2025
- DOI
- 10.1126/science.adv5572