9ZRX

Cryo-EM structure of SHIV-elicited CE79-1571 Fab in complex with HIV Env trimer Q23-SCT27

Summary for 9ZRX

• Entry DOI: 10.2210/pdb9zrx/pdb
• EMDB information: 74654
• Descriptor: CE79-1571 heavy chain, 2-acetamido-2-deoxy-beta-D-glucopyranose, CE79-1571 light chain, ... (10 entities in total)
• Functional Keywords: neutralizing antibody, hiv v2 apex, shiv-elicited, immune complex, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Macaca mulatta; More
• Total number of polymer chains: 8
• Total formula weight: 299014.81

Authors

Roark, R.S.,Shapiro, L.,Kwong, P.D. (deposition date: 2025-12-21, release date: 2026-06-03, Last modification date: 2026-07-22)

Primary citation

Marchitto, L.,Wagh, K.,Roark, R.S.,Coleon, S.,Li, H.,Skelly, A.N.,Hogarty, M.P.,Habib, R.,Ding, W.,Ayyanathan, K.,Liu, W.,Sheng, Z.,Guo, Y.,Bal, J.,Smith, L.M.,Sutherland, L.L.,Park, Y.,Connell, A.J.,Bibollet-Ruche, F.,Lewis, E.,Plante, S.J.,Akeley, M.J.,Lora, J.,Zhao, C.,Carey, J.W.,Martella, C.L.,Li, Y.,Campion, M.S.,Lituchy, M.G.,Osbaldeston, R.A.,Gordon, C.G.,Albertus, A.,Su, J.,Noguchi, C.,Tam, Y.K.,Barbosa, C.,Liang, B.,Amereh, K.,Li, X.,Walsh, A.A.,Irvine, D.J.,Andrabi, R.,Edwards, R.J.,Kreider, E.F.,Weissman, D.,Shapiro, L.,Kwong, P.D.,Korber, B.T.,Haynes, B.F.,Saunders, K.O.,Hahn, B.H.,Shaw, G.M.
Enhanced B cell priming induces broadly neutralizing HIV-1 apex antibodies.
Nature, 2026

PubMed Abstract: Efficient priming of B cell precursors is a rate-limiting step in the induction of V2 apex broadly neutralizing antibodies (bNAbs). Here, we describe a novel germline-targeted HIV-1 Env (CAP256.OPT4) that increases the efficiency of V2 apex bNAb precursor priming by 30-400 fold compared with wild-type HIV-1 Envs and induces - in >90% of macaques - neutralization breadth that includes N130-containing viruses. Using three different delivery platforms - persistently replicating simian human immunodeficiency viruses (SHIVs), protein nanoparticles, and mRNA - we show bNAb priming as early as 4 weeks post-infection or immunization, and neutralization breadth in plasma by 12 weeks. In 14 SHIV-infected macaques, neutralization breadth reached as high as 90% on a 21-virus panel with potency as great as 1:20,000 (50% inhibitory dilution, ID). Monoclonal bNAbs isolated from these animals were similarly broad and potent, with cryo-EM structures representing three distinct lineages revealing canonical needle-like HCDR3 binding. Env-Ab coevolution and structural analyses identified five key residues and loop features under positive selection and temporally associated with neutralization breadth. Importantly, prime-boost immunogens designed to capture these features induced broad and potent neutralization of globally diverse viruses including those containing N130 glycan. Further, rhesus bNAbs were not restricted to IGHD3-15*01 heavy chain alleles. These results expand the utility of the rhesus model for HIV-1 vaccine design and provide a molecular blueprint for inducing V2 apex bNAbs in rhesus and humans.

PubMed: 42380659
DOI: 10.1038/s41586-026-10838-4

Experimental method

ELECTRON MICROSCOPY (3.3 Å)