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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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