Vaccination elicits HIV broadly neutralizing antibodies in primates
18 affiliations
- 1Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA, USA
- 2Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
- 3IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA
- 4Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, USA
- 5Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA
- 6Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- 7Emory National Primate Research Center and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA
- 8The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA
- 9Regeneron Pharmaceuticals, Tarrytown, NY, USA
- 10Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
- 11Howard Hughes Medical Institute, Chevy Chase, MD, USA
- 12Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, USA. [email protected]
- 13Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA, USA. [email protected]
- 14Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego, La Jolla, CA, USA. [email protected]
- 15Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA, USA. [email protected]
- 16Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA. [email protected]
- 17IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA. [email protected]
- 18Moderna, Cambridge, MA, USA. [email protected]
Abstract
The high antigenic diversity of HIV has been a major obstacle to development of a broadly protective vaccine. Nevertheless, protective HIV broadly neutralizing antibodies (bnAbs) exist and have been proposed as templates for vaccine development 1-6 . Germline-targeting is a conceptually radical vaccine design approach to elicit bnAbs, aiming to prime rare bnAb-precursor B cells possessing pre-determined human genetic and structural features shared with template bnAbs, and then guide B cell affinity maturation to potent bnAb evolution with heterologous boosters 7-11 . Although the approach has shown promise in clinical 12-17 and pre-clinical 18-34 studies, it faces many immunological challenges and, to date, has not succeeded in generating bnAbs in humans or nontransgenic animals. Here, we report an adjuvanted protein germline-targeting vaccine tested in outbred nonhuman primates that generated bnAb-class memory B cells and sera capable of neutralizing diverse HIV clinical isolates. bnAb lineages were generated in ≥50% of animals, achieving up to 67% neutralization breadth compared to the reference bnAb. Vaccine-induced bnAbs exhibited precise structural mimicry of human bnAb interactions with HIV envelope (Env), matching the germline-targeting predictions. Furthermore, serum bnAb activity developed in 44% of animals and in the most striking instance reached titers expected to confer protection against diverse HIV isolates. These results demonstrate proof of principle that germline-targeting vaccines can reproducibly elicit prespecified classes of bnAbs to prespecified epitopes under endogenous conditions, supporting further optimization of this approach for HIV vaccine development.
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BibTeX
@article{steichen2026vaccination,
title = {{Vaccination elicits HIV broadly neutralizing antibodies in primates}},
author = {Jon M. Steichen and Patrick J. Madden and Claudia T. Flynn and Swastik Phulera and Monolina Shil and Oleksandr Kalyuzhniy and Alessia Liguori and Carolyne Kifude and Leigh M. Sewall and Christopher A. Cottrell and M. Krystal and Sabyasachi Baboo and Jolene K. Diedrich and Katherine McKenney and Allan C. deCamp and Diane G. Carnathan and Ivy Phung and Parham Ramezani-Rad and Ester Marina-Zárate and Brian Freeman and Zhenfei Xie and Jeong Hyun Lee and Troy Sincomb and Nicole Phelps and Danny Lu and Diana Goodwin and Ryan D. Tingle and Yumiko Adachi and Nushin B. Alavi and Jenny Tran and Andy S. Tran and Alyne Nascimento and Catherine Sovie and Daniel L. Bader and Hannah Voic and Xiaoya Zhou and Grace Pixton and Agnes A. Walsh and Mariane B. Melo and Torben Schiffner and Facundo D. Batista and Dennis R. Burton and Darrell J. Irvine and James C. Paulson and John R. Yates and Gabriel Ozorowski and Andrew B. Ward and Guido Silvestri and Shane Crotty and William R. Schief},
journal = {Nature},
year = {2026},
month = jun,
doi = {10.1038/s41586-026-10837-5},
url = {https://doi.org/10.1038/s41586-026-10837-5},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Vaccination elicits HIV broadly neutralizing antibodies in primates
AU - Jon M. Steichen
AU - Patrick J. Madden
AU - Claudia T. Flynn
AU - Swastik Phulera
AU - Monolina Shil
AU - Oleksandr Kalyuzhniy
AU - Alessia Liguori
AU - Carolyne Kifude
AU - Leigh M. Sewall
AU - Christopher A. Cottrell
AU - M. Krystal
AU - Sabyasachi Baboo
AU - Jolene K. Diedrich
AU - Katherine McKenney
AU - Allan C. deCamp
AU - Diane G. Carnathan
AU - Ivy Phung
AU - Parham Ramezani-Rad
AU - Ester Marina-Zárate
AU - Brian Freeman
AU - Zhenfei Xie
AU - Jeong Hyun Lee
AU - Troy Sincomb
AU - Nicole Phelps
AU - Danny Lu
AU - Diana Goodwin
AU - Ryan D. Tingle
AU - Yumiko Adachi
AU - Nushin B. Alavi
AU - Jenny Tran
AU - Andy S. Tran
AU - Alyne Nascimento
AU - Catherine Sovie
AU - Daniel L. Bader
AU - Hannah Voic
AU - Xiaoya Zhou
AU - Grace Pixton
AU - Agnes A. Walsh
AU - Mariane B. Melo
AU - Torben Schiffner
AU - Facundo D. Batista
AU - Dennis R. Burton
AU - Darrell J. Irvine
AU - James C. Paulson
AU - John R. Yates
AU - Gabriel Ozorowski
AU - Andrew B. Ward
AU - Guido Silvestri
AU - Shane Crotty
AU - William R. Schief
PY - 2026
DA - 2026/06/30
JO - Nature
DO - 10.1038/s41586-026-10837-5
UR - https://doi.org/10.1038/s41586-026-10837-5
AB - The high antigenic diversity of HIV has been a major obstacle to development of a broadly protective vaccine. Nevertheless, protective HIV broadly neutralizing antibodies (bnAbs) exist and have been proposed as templates for vaccine development 1-6 . Germline-targeting is a conceptually radical vaccine design approach to elicit bnAbs, aiming to prime rare bnAb-precursor B cells possessing pre-determined human genetic and structural features shared with template bnAbs, and then guide B cell affinity maturation to potent bnAb evolution with heterologous boosters 7-11 . Although the approach has shown promise in clinical 12-17 and pre-clinical 18-34 studies, it faces many immunological challenges and, to date, has not succeeded in generating bnAbs in humans or nontransgenic animals. Here, we report an adjuvanted protein germline-targeting vaccine tested in outbred nonhuman primates that generated bnAb-class memory B cells and sera capable of neutralizing diverse HIV clinical isolates. bnAb lineages were generated in ≥50% of animals, achieving up to 67% neutralization breadth compared to the reference bnAb. Vaccine-induced bnAbs exhibited precise structural mimicry of human bnAb interactions with HIV envelope (Env), matching the germline-targeting predictions. Furthermore, serum bnAb activity developed in 44% of animals and in the most striking instance reached titers expected to confer protection against diverse HIV isolates. These results demonstrate proof of principle that germline-targeting vaccines can reproducibly elicit prespecified classes of bnAbs to prespecified epitopes under endogenous conditions, supporting further optimization of this approach for HIV vaccine development.
SN - 0028-0836
SN - 1476-4687
ER -