9PQ3

Cryo-EM structure of HIV-1 459C-ALT DS-SOSIP RnS Env trimer

Summary for 9PQ3

• Entry DOI: 10.2210/pdb9pq3/pdb
• EMDB information: 71782
• Descriptor: HIV-1 459C-ALT RnS DS-SOSIP gp41, HIV-1 459C-ALT RnS DS-SOSIP gp120, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: envelope trimer, 459c-alt, rns ds-sosip immunogen, viral protein
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 6
• Total formula weight: 240758.85

Authors

Wang, S.,Zhou, T.,Kwong, P.D.,Morano, N.C.,Shapiro, L. (deposition date: 2025-07-22, release date: 2025-12-17, Last modification date: 2026-02-18)

Primary citation

Duan, H.,Nkolola, J.P.,Wang, S.,Chaudhari, J.,Teng, I.T.,Lavine, C.,Parchment, D.K.,Sellers, G.S.,McKee, K.,O'Dell, S.,Choe, M.,Du, H.,Zhang, B.,Perez, A.A.E.,Rossler, A.,Lasrado, N.,Biju, A.,Becker, J.E.,Carroll, R.,Carson, A.S.,Henry, A.R.,Morano, N.C.,Mughal, M.,Rawi, R.,Roark, R.S.,Schramm, C.A.,Shen, C.H.,Smith, S.C.,Stephens, T.,Tsybovsky, Y.,Van Wazer, D.J.,Wang, H.,Yang, Y.,Rutten, L.,Langedijk, J.P.M.,Cheng, C.,Wang, L.,Douek, D.C.,Koup, R.A.,Mascola, J.R.,Shapiro, L.,Zhou, T.,Doria-Rose, N.A.,Korber, B.,Seaman, M.S.,Pierson, T.C.,Kwong, P.D.,Barouch, D.H.
Vaccine elicitation of HIV-1 neutralizing antibodies against both V2 apex and fusion peptide in rhesus macaques.
Cell Rep, 45:116905-116905, 2026

PubMed Abstract: Broadly neutralizing antibodies (bNAbs) targeting multiple sites of HIV-1 Env vulnerability can be induced by infection, but simultaneous elicitation of bNAbs against multiple epitopes has not been achieved by vaccination. In this study, we designed a dual-epitope vaccine targeting both the fusion peptide (FP) and the V2 apex and evaluated its capacity to induce bNAbs against both epitopes in rhesus macaques. This vaccine combined an FP conjugate with a cocktail of engineered Env trimers with enhanced V2 apex recognition and increased antigen retention in lymph nodes. Macaque immunization with the dual-epitope vaccine elicited >1,000-fold higher autologous tier 2-neutralizing titers than wild-type Env trimers and enhanced heterologous neutralization. Both FP- and V2 apex-monoclonal antibodies were isolated from immunized macaques and showed heterologous neutralization with genetic and structural signatures similar to well-characterized FP and V2 apex bNAbs. These results demonstrate proof of concept for simultaneous vaccine elicitation of neutralizing antibodies against multiple sites of Env vulnerability.

PubMed: 41615799
DOI: 10.1016/j.celrep.2025.116905

Experimental method

ELECTRON MICROSCOPY (3.94 Å)