Download MendeleyPrecise targeting of HIV broadly neutralizing antibody precursors in humans.
Caniels, T.G., Prabhakaran, M., Ozorowski, G., MacPhee, K.J., Wu, W., van der Straten, K., Agrawal, S., Derking, R., Reiss, E.I.M.M., 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 Jr., K.N., 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.(2025) Science : eadv5572-eadv5572
- PubMed: 40373114
- DOI: https://doi.org/10.1126/science.adv5572
- Primary Citation of Related Structures:
9MI0, 9MIA, 9MIB, 9MIH, 9MII - PubMed 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, 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.
Organizational Affiliation:
Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, location AMC, Amsterdam, Netherlands.
