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

Tom G. Caniels; Madhu S. Prabhakaran; Sashank Agrawal; Kellie J. MacPhee; Rhianna Bronson; Weiwei Wu; Eva I.M. Schumacher; Swastik Phulera; Katrina G. Millard; Deanna Dong; Martina Turroja; Aimee A. Desrosiers; Jeffrey Michael Bethony; Elissa M. Malkin; Annelou van der Veen; Karlijn van der Straten; Michelle J. Klouwens; Suprabhath R. Gajjala; Nicole L. Yates; Katrina Saam; Andy S. Tran; Meghna Chandrasekar; Alison Benner; Zahra Rikhtegaran Tehrani; Mukundhan Ramaswami; Jonne L. Snitselaar; Tom P. L. Bijl; Judith A. Burger; Jacqueline van Rijswijk; Joey H. Bouhuijs

doi:10.64898/2026.10.21.760679

ImmunologybioRxivOct 26, 2026

Preprint

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

Tom G. Caniels iD, Madhu S. Prabhakaran iD, Sashank Agrawal iD, Kellie J. MacPhee iD, Rhianna Bronson iD, Weiwei Wu iD, Eva I.M. Schumacher, Swastik Phulera iD, Katrina G. Millard iD, Deanna Dong, Martina Turroja iD, Aimee A. Desrosiers iD, Jeffrey Michael Bethony iD, Elissa M. Malkin iD, Annelou van der Veen, Karlijn van der Straten iD, Michelle J. Klouwens iD, Suprabhath R. Gajjala iD, Nicole L. Yates iD, Katrina Saam, Andy S. Tran iD, Meghna Chandrasekar, Alison Benner iD, Zahra Rikhtegaran Tehrani iD, Mukundhan Ramaswami, , Rogier W. Sanders iD

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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.