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
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>