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Precise targeting of HIV broadly neutralizing antibody precursors in humans

May-25

Journal Article

Authors:

Caniels, T. G.
Prabhakaran, M.
Ozorowski, G.
MacPhee, K. J.
Wu, W.
van der Straten, K.
Agrawal, S.
Derking, R.
Reiss, Eimm
Millard, K.
Turroja, M.
Desrosiers, A.
Bethony, J.
Malkin, E.
Liesdek, M. H.
van der Veen, A.
Klouwens, M.
Snitselaar, J. L.
Bouhuijs, J. H.
Bronson, R.
Jean-Baptiste, J.
Gajjala, S.
Rikhtegaran Tehrani, Z.
Benner, A.
Ramaswami, M.
Duff, M. O.
Liu, Y. W.
Sato, A. H.
Kim, J. Y.
Baken, I. J. L.
Mendes Silva, C.
Bijl, T. P. L.
van Rijswijk, J.
Burger, J. A.
Cupo, A.
Yasmeen, A.
Phulera, S.
Lee, W. H.
Randall, K. N., Jr.
Zhang, S.
Corcoran, M. M.
Regadas, I.
Sullivan, A. C.
Brown, D. M.
Bohl, J. A.
Greene, K. M.
Gao, H.
Yates, N. L.
Sawant, S.
Prins, J. M.
Kootstra, N. A.
Kaminsky, S. M.
Barin, B.
Rahaman, F.
Meller, M.
Philiponis, V.
Laufer, D. S.
Lombardo, A.
Mwoga, L.
Shotorbani, S.
Holman, D.
Koup, R. A.
Klasse, P. J.
Karlsson Hedestam, G. B.
Tomaras, G. D.
van Gils, M. J.
Montefiori, D. C.
McDermott, A. B.
Hyrien, O.
Moore, J. P.
Wilson, I. A.
Ward, A. B.
Diemert, D. J.
de Bree, G. J.
Andrews, S. F.
Caskey, M.
Sanders, R. W.

Journal:
Science

PMID:
40373114

URL:
https://www.ncbi.nlm.nih.gov/pubmed/40373114

DOI:
10.1126/science.adv5572

Keywords:
humans HIV vaccine CD4 neutralizing antibody

Abstract:
<p>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, that 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.</p>

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