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TitleVaccine elicitation of HIV-1 neutralizing antibodies against both V2 apex and fusion peptide in rhesus macaques.
Journal, issue, pagesCell Rep, Vol. 45, Issue 2, Page 116905, Year 2026
Publish dateJan 28, 2026
AuthorsHongying Duan / Joseph P Nkolola / Shuishu Wang / Jayeshbhai Chaudhari / I-Ting Teng / Christy Lavine / Danealle K Parchment / George S Sellers / Krisha McKee / Sijy O'Dell / Misook Choe / Haijuan Du / Baoshan Zhang / Alejandro A Espinosa Perez / Annika Rossler / Ninaad Lasrado / Andrea Biju / Jordan E Becker / Robin Carroll / Audrey S Carson / Amy R Henry / Nicholas C Morano / Madeeha Mughal / Reda Rawi / Ryan S Roark / Chaim A Schramm / Chen-Hsiang Shen / Sarah C Smith / Tyler Stephens / Yaroslav Tsybovsky / David J Van Wazer / Hua Wang / Yongping Yang / Lucy Rutten / Johannes P M Langedijk / Cheng Cheng / Lingshu Wang / Daniel C Douek / Richard A Koup / John R Mascola / Lawrence Shapiro / Tongqing Zhou / Nicole A Doria-Rose / Bette Korber / Michael S Seaman / Theodore C Pierson / Peter D Kwong / Dan H Barouch /
PubMed AbstractBroadly 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 ...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.
External linksCell Rep / PubMed:41615799
MethodsEM (single particle)
Resolution3.01 - 3.94 Å
Structure data

71766

9pni

EMDB-71766, PDB-9pni:
Cryo-EM structure of J601-1B2 Fab in complex with HIV-1 BG505 DS-SOSIP Env trimer
Method: EM (single particle) / Resolution: 3.83 Å

71767

9pnn

EMDB-71767, PDB-9pnn:
Cryo-EM structure of J601-A6 Fab in complex with HIV-1 BG505 DS-SOSIP Env trimer
Method: EM (single particle) / Resolution: 3.5 Å

71772

9pnu

EMDB-71772, PDB-9pnu:
Cryo-EM structure of K001-A1 Fab in complex with HIV-1 459C-OPT RnS DS-SOSIP Env trimer
Method: EM (single particle) / Resolution: 3.01 Å

71781

9pq2

EMDB-71781, PDB-9pq2:
Cryo-EM structure of HIV-1 459C-WT DS-SOSIP RnS Env trimer
Method: EM (single particle) / Resolution: 3.33 Å

71782

9pq3

EMDB-71782, PDB-9pq3:
Cryo-EM structure of HIV-1 459C-ALT DS-SOSIP RnS Env trimer
Method: EM (single particle) / Resolution: 3.94 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-MAN:
alpha-D-mannopyranose

Source
  • human immunodeficiency virus 1
  • macaca mulatta (Rhesus monkey)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / antibody-antigen complex / fusion peptide directed / viral surface glycoprotein / ANTIVIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / V2-directed antibody / VIRAL PROTEIN / Envelope trimer / 459C-WT / RnS DS-SOSIP immunogen / 459C-ALT

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