Precise targeting of HIV broadly neutralizing antibody precursors in humans
- Tom G. Caniels
- Madhu Prabhakaran
- Gabriel Ozorowski
- Kellie J. MacPhee
- Weiwei Wu
- Karlijn van der Straten
- Sashank Agrawal
- Ronald Derking
- Emma I. M. M. Reiss
- Katrina Millard
- Martina Turroja
- Aimee Desrosiers
- Jeffrey Bethony
- Elissa Malkin
- Marinus H. Liesdek
- Annelou van der Veen
- Michelle Klouwens
- Jonne L. Snitselaar
- Joey H. Bouhuijs
- Rhianna Bronson
- Jalen Jean-Baptiste
- Suprabhath Gajjala
- Zahra Rikhtegaran Tehrani
- Alison Benner
- Mukundhan Ramaswami
- Michael O. Duff
- Yung-Wen Liu
- Alicia H. Sato
- Ju Yeong Kim
- Isabel J. L. Baken
- Catarina Mendes Silva
- Tom P. L. Bijl
- Jacqueline van Rijswijk
- Judith A. Burger
- Albert Cupo
- Anila Yasmeen
- Swastik Phulera
- Wen-Hsin Lee
- Kipchoge N. Randall
- Shiyu Zhang
- Martin M. Corcoran
- Isabel Regadas
- Alex C. Sullivan
- David M. Brown
- Jennifer A. Bohl
- Kelli M. Greene
- Hongmei Gao
- Nicole L. Yates
- Sheetal Sawant
- Jan M. Prins
2025-05-15
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, which 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.