9YML

RRr20_wk72_07 Fab in complex with BG505 MD39 SOSIP and RM20A3 Fab

Summary for 9YML

• Entry DOI: 10.2210/pdb9yml/pdb
• EMDB information: 73110
• Descriptor: RM20A3 Fab heavy chain, 2-acetamido-2-deoxy-beta-D-glucopyranose, RRr20_wk72_07 Fab heavy chain, ... (10 entities in total)
• Functional Keywords: hiv-1, env, nhp, v3 glycan, bg18, germline targeting, viral protein-immune system complex, viral protein/immune system
• Biological source: Macaca mulatta (Rhesus monkey); More
• Total number of polymer chains: 18
• Total formula weight: 531259.48

Authors

Phulera, S.,Ozorowski, G.,Ward, A.B. (deposition date: 2025-10-10, release date: 2026-07-08, Last modification date: 2026-08-26)

Primary citation

Steichen, J.M.,Madden, P.J.,Flynn, C.T.,Phulera, S.,Shil, M.,Kalyuzhniy, O.,Liguori, A.,Kifude, C.,Sewall, L.M.,Cottrell, C.A.,Ma, K.M.,Baboo, S.,Diedrich, J.K.,McKenney, K.,deCamp, A.C.,Carnathan, D.G.,Phung, I.,Ramezani-Rad, P.,Marina-Zarate, E.,Freeman, B.,Xie, Z.,Lee, J.H.,Sincomb, T.,Phelps, N.,Lu, D.,Goodwin, D.,Tingle, R.,Adachi, Y.,Alavi, N.,Tran, J.,Tran, A.S.,Nascimento, A.,Sovie, C.,Bader, D.L.V.,Voic, H.,Zhou, X.,Pixton, G.,Walsh, A.,Melo, M.B.,Schiffner, T.,Batista, F.D.,Burton, D.R.,Irvine, D.J.,Paulson, J.C.,Yates 3rd, J.R.,Ozorowski, G.,Ward, A.B.,Silvestri, G.,Crotty, S.,Schief, W.R.
Vaccination elicits HIV broadly neutralizing antibodies in primates.
Nature, 656:723-733, 2026

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 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.

PubMed: 42380658
DOI: 10.1038/s41586-026-10837-5

Experimental method

ELECTRON MICROSCOPY (3.2 Å)