9OMG

Cryo-EM structure of rhesus antibody V033-a.I1 in complex with HIV Env trimer Q23.17 MD39

Summary for 9OMG

• Entry DOI: 10.2210/pdb9omg/pdb
• EMDB information: 70613
• Descriptor: HIV Env gp120, 2-acetamido-2-deoxy-beta-D-glucopyranose, HIV Env gp41 ectodomain, ... (10 entities in total)
• Functional Keywords: neutralizing antibody, hiv-1 v2 apex, shiv-elicited, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 8
• Total formula weight: 285380.15

Authors

Roark, R.S.,Shapiro, L.,Kwong, P.D. (deposition date: 2025-05-13, release date: 2025-11-05, Last modification date: 2026-02-25)

Primary citation

Habib, R.,Roark, R.S.,Li, H.,Connell, A.J.,Hogarty, M.P.,Wagh, K.,Wang, S.,Marchitto, L.,Skelly, A.N.,Carey, J.W.,Sowers, K.J.,Ayyanathan, K.,Plante, S.J.,Bibollet-Ruche, F.,Park, Y.,Agostino, C.J.,Singh, A.,Martella, C.L.,Lewis, E.,Rando, J.M.,Chohan, N.,Lora, J.,Ding, W.,Campion, M.S.,Zhao, C.,Liu, W.,Li, Y.,Li, X.,Liang, B.,Chowdhury, R.R.,Amereh, K.,Van Itallie, E.,Sheng, Z.,Ghosh, A.R.,Bar, K.J.,Williams, W.B.,Wiehe, K.,Saunders, K.O.,Edwards, R.J.,Cain, D.W.,Lewis, M.G.,Batista, F.D.,Burton, D.R.,Andrabi, R.,Kulp, D.W.,Haynes, B.F.,Korber, B.,Shapiro, L.,Kwong, P.D.,Hahn, B.H.,Shaw, G.M.
Env-antibody coevolution identifies B cell priming as the principal bottleneck to HIV V2 apex broadly neutralizing antibody development.
Sci Immunol, 11:eadz3933-eadz3933, 2026

PubMed Abstract: Broadly neutralizing antibodies (bNAbs) are rarely elicited during HIV-1 infection. To identify obstacles to bNAb development, we longitudinally studied 122 rhesus macaques infected by 1 of 16 different simian-human immunodeficiency viruses (SHIVs). We identified the V2 apex region of the envelope (Env) as the most common bNAb target and a subset of Envs that preferentially elicited these antibodies. In 10 macaques, we delineated Env-antibody coevolution from B cell priming to bNAb development. Antibody phylogenies revealed permissive developmental pathways guided by evolving Envs that contained few mutations in or near the V2 apex C-strand, which were a sensitive indicator of apex-targeted responses. The absence of such mutations reflected a failure in bNAb priming. These results indicate that efficiency of B cell priming, and not complexities in Env-guided affinity maturation, is a primary obstacle to V2 apex bNAb elicitation in SHIV-infected macaques and identify specific HIV-1 Envs to advance as vaccine platforms.

PubMed: 41686912
DOI: 10.1126/sciimmunol.adz3933

Experimental method

ELECTRON MICROSCOPY (3.6 Å)