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| Title | Vaccination elicits HIV broadly neutralizing antibodies in primates. |
|---|---|
| Journal, issue, pages | Nature, Year 2026 |
| Publish date | Jun 30, 2026 |
 Authors | Jon M Steichen / Patrick J Madden / Claudia T Flynn / Swastik Phulera / Monolina Shil / Oleksandr Kalyuzhniy / Alessia Liguori / Carolyne Kifude / Leigh M Sewall / Christopher A Cottrell / Krystal M Ma / Sabyasachi Baboo / Jolene K Diedrich / Katherine McKenney / Allan C deCamp / Diane G Carnathan / Ivy Phung / Parham Ramezani-Rad / Ester Marina-Zárate / Brian Freeman / Zhenfei Xie / Jeong Hyun Lee / Troy Sincomb / Nicole Phelps / Danny Lu / Diana Goodwin / Ryan Tingle / Yumiko Adachi / Nushin Alavi / Jenny Tran / Andy S Tran / Alyne Nascimento / Catherine Sovie / Daniel L V Bader / Hannah Voic / Xiaoya Zhou / Grace Pixton / Agnes Walsh / Mariane B Melo / Torben Schiffner / Facundo D Batista / Dennis R Burton / Darrell J Irvine / James C Paulson / John R Yates / Gabriel Ozorowski / Andrew B Ward / Guido Silvestri / Shane Crotty / William R Schief /  |
| PubMed 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 ...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. 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. Although the approach has shown promise in clinical and pre-clinical 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. |
 External links | Nature / PubMed:42380658 |
| Methods | EM (single particle) |
| Resolution | 2.7 - 3.4 Å |
| Structure data | EMDB-73108, PDB-9ymj: EMDB-73109, PDB-9ymk: EMDB-73110, PDB-9yml: |
| Chemicals |  ChemComp-NAG: |
| Source |
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 Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 / Env / NHP / V3 glycan / BG18 / germline targeting / VIRAL PROTEIN-IMMUNE SYSTEM complex |
human immunodeficiency virus 1
homo sapiens (human)
macaca mulatta (Rhesus monkey)