9YHS

AM12-340 Fab in complex with HIV-1 Env 5MUT-3fill SOSIP

Summary for 9YHS

• Entry DOI: 10.2210/pdb9yhs/pdb
• Related: 9YHR
• EMDB information: 72972
• Descriptor: AM12-340 Fab heavy chain, 2-acetamido-2-deoxy-beta-D-glucopyranose, AM12-340 Fab light chain, ... (10 entities in total)
• Functional Keywords: hiv-1, envelope protein, vaccine, immunogen, antibody, bnab, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Macaca mulatta (Rhesus monkey); More
• Total number of polymer chains: 12
• Total formula weight: 320170.48

Authors

Gristick, H.B.,Gavor, E.,Bjorkman, P.J. (deposition date: 2025-09-30, release date: 2026-06-10)

Primary citation

Skelly, A.N.,Gristick, H.B.,Li, H.,Gavor, E.,Connell, A.J.,Kreider, E.F.,Marchitto, L.,Hogarty, M.P.,Newby, M.L.,Allen, J.D.,Liu, W.,West Jr., A.P.,Ayyanathan, K.,Campion, M.S.,Winters, K.,Gordon, C.G.,Osbaldeston, R.A.,Akeley, M.J.,Lewis, E.,Li, Y.,Singh, A.,Cruickshank, K.,Park, Y.,Zhao, C.,Li, X.,Amereh, K.,Van Itallie, E.,Carey, J.W.,Albertus, A.,DeLaitsch, A.T.,Keeffe, J.R.,Lituchy, M.G.,Walsh, A.A.,Morris, D.J.,Habib, R.,Bibollet-Ruche, F.,Mishra, N.,Avillion, G.,Koranda, N.S.,Plante, S.J.,Martella, C.L.,Lora, J.,Wang, E.J.D.,Lewis, M.G.,Martin, M.A.,Nussenzweig, M.C.,Seaman, M.S.,Irvine, D.J.,Wiehe, K.J.,Haynes, B.F.,Wagh, K.,Korber, B.,Andrabi, R.,Crispin, M.,Weissman, D.,Bjorkman, P.J.,Hahn, B.H.,Shaw, G.M.
Induction of broadly neutralizing HIV antibodies by a two-step mechanism informs vaccine design.
Science, :eaec6396-eaec6396, 2026

PubMed Abstract: A major obstacle confronting HIV-1 vaccine and cure research is the lack of an outbred animal model for rapid and consistent induction of broadly neutralizing antibodies (bNAbs). We designed an epitope-focused simian-human immunodeficiency virus (SHIV.5MUT) that elicited broad and potent V3-glycan-targeted antibodies within a year of infection in 14 of 22 macaques compared with 0 of 14 control animals. SHIV.5MUT elicited bNAbs by a two-step mechanism, inducing an initial wave of V1-directed antibodies that selected for Envs with shortened, hypoglycosylated V1 loops, which in turn primed V3-glycan bNAb precursors. Rhesus bNAbs were immunogenetically and structurally diverse, closely resembling human V3-glycan bNAbs. Env-bNAb coevolution revealed a diverse repertoire of bNAb precursors and the Env variants that matured them, yielding a molecular blueprint for vaccine design.

PubMed: 42096521
DOI: 10.1126/science.aec6396

Experimental method

ELECTRON MICROSCOPY (4.3 Å)