PreprintCC BYbioRxiv
Sequential vaccination matures VRC01-class HIV-1 neutralizing antibodies in humans
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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BibTeX
@misc{caniels2026sequential,
title = {{Sequential vaccination matures VRC01-class HIV-1 neutralizing antibodies in humans}},
author = {Tom G. Caniels and Madhu Prabhakaran and Sashank Agrawal and Kellie J. MacPhee and Rhianna Bronson and Weiwei Wu and Eva I.M. Schumacher and Swastik Phulera and Katrina Millard and Deanna Dong and Martina Turroja and Aimee Desrosiers and Jeffrey Bethony and Elissa Malkin and Annelou van der Veen and Karlijn van der Straten and Michelle Klouwens and Suprabhath Gajjala and Nicole L. Yates and Katrina Saam and Andy S. Tran and Meghna Chandrasekar and Alison Benner and Zahra Rikhtegaran Tehrani and Mukundhan Ramaswami and Jonne L. Snitselaar and Tom P.L. Bijl and Judith A. Burger and Jacqueline van Rijswijk and Joey H. Bouhuijs and Albert Cupo and Michael O. Duff and Alicia H. Sato and Isabel J.L. Baken and Catarina Mendes Silva and Jennifer A. Bohl and David M. Brown and Alex C. Sullivan and Kelli M. Greene and Hongmei Gao and Sheetal Sawant and Agnes M. Harskamp and Neeltje A. Kootstra and Burc Barin and Vince Philiponis and Lebohang Molife and Annie F. Mabushi and Dagna S. Laufer and Angela Lombardo and Claudio Yurdadon and Ethan A. Wilson and Ju Yeong Kim and Lindsey Mwoga and Solmaz Shotorbani and Drienna Holman and Marit J. van Gils and Per Johan Klasse and Sarah F. Andrews and Richard A. Koup and Georgia D. Tomaras},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.21.760679},
url = {https://www.biorxiv.org/content/10.64898/2026.10.21.760679v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Sequential vaccination matures VRC01-class HIV-1 neutralizing antibodies in humans
AU - Tom G. Caniels
AU - Madhu Prabhakaran
AU - Sashank Agrawal
AU - Kellie J. MacPhee
AU - Rhianna Bronson
AU - Weiwei Wu
AU - Eva I.M. Schumacher
AU - Swastik Phulera
AU - Katrina Millard
AU - Deanna Dong
AU - Martina Turroja
AU - Aimee Desrosiers
AU - Jeffrey Bethony
AU - Elissa Malkin
AU - Annelou van der Veen
AU - Karlijn van der Straten
AU - Michelle Klouwens
AU - Suprabhath Gajjala
AU - Nicole L. Yates
AU - Katrina Saam
AU - Andy S. Tran
AU - Meghna Chandrasekar
AU - Alison Benner
AU - Zahra Rikhtegaran Tehrani
AU - Mukundhan Ramaswami
AU - Jonne L. Snitselaar
AU - Tom P.L. Bijl
AU - Judith A. Burger
AU - Jacqueline van Rijswijk
AU - Joey H. Bouhuijs
AU - Albert Cupo
AU - Michael O. Duff
AU - Alicia H. Sato
AU - Isabel J.L. Baken
AU - Catarina Mendes Silva
AU - Jennifer A. Bohl
AU - David M. Brown
AU - Alex C. Sullivan
AU - Kelli M. Greene
AU - Hongmei Gao
AU - Sheetal Sawant
AU - Agnes M. Harskamp
AU - Neeltje A. Kootstra
AU - Burc Barin
AU - Vince Philiponis
AU - Lebohang Molife
AU - Annie F. Mabushi
AU - Dagna S. Laufer
AU - Angela Lombardo
AU - Claudio Yurdadon
AU - Ethan A. Wilson
AU - Ju Yeong Kim
AU - Lindsey Mwoga
AU - Solmaz Shotorbani
AU - Drienna Holman
AU - Marit J. van Gils
AU - Per Johan Klasse
AU - Sarah F. Andrews
AU - Richard A. Koup
AU - Georgia D. Tomaras
PY - 2026
DA - 2026/10/21
PB - bioRxiv
DO - 10.64898/2026.10.21.760679
UR - https://www.biorxiv.org/content/10.64898/2026.10.21.760679v1
AB - 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.
SN - 2692-8205
ER -