Sequential vaccination matures VRC01-class HIV-1 neutralizing antibodies in humans

Caniels, T. G.; Prabhakaran, M.; Agrawal, S.; MacPhee, K. J.; Bronson, R.; Wu, W.; Schumacher, E. I. M.; Phulera, S.; Millard, K.; Dong, D.; Turroja, M.; Desrosiers, A.; Bethony, J.; Malkin, E.; van der Veen, A.; van der Straten, K.; Klouwens, M.; Gajjala, S.; Yates, N. L.; Saam, K.; Tran, A. S.; Chandrasekar, M.; Benner, A.; Rikhtegaran Tehrani, Z.; Ramaswami, M.; Snitselaar, J. L.; Bijl, T. P. L.; Burger, J. A.; van Rijswijk, J.; Bouhuijs, J. H.; Cupo, A.; Duff, M. O.; Sato, A. H.; Baken, I. J. L.; Mendes Silva, C.; Bohl, J. A.; Brown, D. M.; Sullivan, A. C.; Greene, K.; Gao, H.; Sawant, S.

doi:10.64898/2026.10.21.760679

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bioRxiv · 10.64898/2026.10.21.760679

Sequential vaccination matures VRC01-class HIV-1 neutralizing antibodies in humans

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Abstract

Inducing a broadly neutralizing antibody (bnAb) response is a key goal of HIV-1 vaccine development. Despite significant progress, it is unknown whether vaccine-primed B cells can be reactivated and matured to secrete bona fide bnAbs. In the IAVI C107/C110 single-arm, open-label human trial, VRC01-class memory B cells previously primed by the GT1.1 germline-targeting envelope glycoprotein (Env) trimer were reactivated by a BG505 SOSIP.664 trimer boost. Somatic hypermutation in the activated B cells drove higher antibody affinity for the CD4-binding site on fully glycosylated, heterologous Env trimers. Three VRC01-class monoclonal antibodies derived from independent B cell lineages neutralized 18-31% of 119 viruses in a globally diverse panel. This work advances the HIV-1 germline-targeting vaccination concept from proof-of-priming towards proof-of-breadth and defines a benchmark for bnAb induction.

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Caniels, T. G., Prabhakaran, M., Agrawal, S., MacPhee, K. J., Bronson, R., Wu, W., Schumacher, E. I. M., Phulera, S., Millard, K., Dong, D., Turroja, M., Desrosiers, A., Bethony, J., Malkin, E., van der Veen, A., van der Straten, K., Klouwens, M., Gajjala, S., Yates, N. L., Saam, K., Tran, A. S., Chandrasekar, M., Benner, A., Rikhtegaran Tehrani, Z., Ramaswami, M., Snitselaar, J. L., Bijl, T. P. L., Burger, J. A., van Rijswijk, J., Bouhuijs, J. H., Cupo, A., Duff, M. O., Sato, A. H., Baken, I. J. L., Mendes Silva, C., Bohl, J. A., Brown, D. M., Sullivan, A. C., Greene, K., Gao, H., Sawant, S.. 2026-10-26. Sequential vaccination matures VRC01-class HIV-1 neutralizing antibodies in humans. https://doi.org/10.64898/2026.10.21.760679

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