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Structure paper

TitleInduction of broadly neutralizing HIV antibodies by a two-step mechanism informs vaccine design.
Journal, issue, pagesScience, Page eaec6396, Year 2026
Publish dateMay 7, 2026
AuthorsAshwin N Skelly / Harry B Gristick / Hui Li / Edem Gavor / Andrew J Connell / Edward F Kreider / Lorie Marchitto / Michael P Hogarty / Maddy L Newby / Joel D Allen / Weimin Liu / Anthony P West / Kasirajan Ayyanathan / Mary S Campion / Kaitlyn Winters / Colette G Gordon / Rebecca A Osbaldeston / Macy J Akeley / Emily Lewis / Yingying Li / Ajay Singh / Kendra Cruickshank / Younghoon Park / Chengyan Zhao / Xuduo Li / Khaled Amereh / Elizabeth Van Itallie / John W Carey / Amie Albertus / Andrew T DeLaitsch / Jennifer R Keeffe / Melinda G Lituchy / Agnes A Walsh / Daniel J Morris / Rumi Habib / Frederic Bibollet-Ruche / Nitesh Mishra / Gabriel Avillion / Nicholas S Koranda / Samantha J Plante / Christian L Martella / Jinery Lora / Eric J D Wang / Mark G Lewis / Malcolm A Martin / Michel C Nussenzweig / Michael S Seaman / Darrell J Irvine / Kevin J Wiehe / Barton F Haynes / Kshitij Wagh / Bette Korber / Raiees Andrabi / Max Crispin / Drew Weissman / Pamela J Bjorkman / Beatrice H Hahn / George M Shaw /
PubMed AbstractA 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 ...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.
External linksScience / PubMed:42096521
MethodsEM (single particle)
Resolution3.0 - 5.0 Å
Structure data

72969

9yho

EMDB-72969, PDB-9yho:
AJ09-21 Fab in complex with HIV-1 Env 5MUT-3fill SOSIP
Method: EM (single particle) / Resolution: 3.2 Å

72970

9yhq

EMDB-72970, PDB-9yhq:
AJ09-83 Fab in complex with HIV-1 Env 5MUT-3fill SOSIP
Method: EM (single particle) / Resolution: 3.0 Å

72971

9yhr

EMDB-72971, PDB-9yhr:
AJ09-110 Fab in complex with HIV-1 Env 5MUT-3fill SOSIP
Method: EM (single particle) / Resolution: 3.1 Å

72973

9yht

EMDB-72973, PDB-9yht:
AM12-347 Fab in complex with HIV-1 Env 5MUT-3fill SOSIP
Method: EM (single particle) / Resolution: 4.3 Å

72985

9yib

EMDB-72985, PDB-9yib:
AM12-351 Fab in complex with HIV-1 Env 5MUT-3fill SOSIP
Method: EM (single particle) / Resolution: 4.3 Å

72986

9yid

EMDB-72986, PDB-9yid:
AM12-352 Fab in complex with HIV-1 Env 5MUT-3fill SOSIP
Method: EM (single particle) / Resolution: 4.5 Å

72987

9yie

EMDB-72987, PDB-9yie:
NN39-25 Fab in complex with HIV-1 Env 5MUT-3fill SOSIP
Method: EM (single particle) / Resolution: 4.3 Å

72988

9yif

EMDB-72988, PDB-9yif:
NN39-171 Fab in complex with HIV-1 Env 5MUT-3fill SOSIP
Method: EM (single particle) / Resolution: 3.8 Å

72989

9yig

EMDB-72989, PDB-9yig:
V634-136 Fab in complex with HIV-1 Env 5MUT-3fill SOSIP
Method: EM (single particle) / Resolution: 3.4 Å

72990

9yih

EMDB-72990, PDB-9yih:
V634-136 UCA Fab in complex with HIV-1 Env del4-3fill SOSIP
Method: EM (single particle) / Resolution: 4.2 Å

72991

9yii

EMDB-72991, PDB-9yii:
V645-158 Fab in complex with HIV-1 Env 5MUT-3fill SOSIP
Method: EM (single particle) / Resolution: 4.2 Å

72992

9yij

EMDB-72992, PDB-9yij:
HIV-1 Env 5MUT-3fill SOSIP
Method: EM (single particle) / Resolution: 4.1 Å

72993

9yik

EMDB-72993, PDB-9yik:
HIV-1 Env del4-3fill SOSIP
Method: EM (single particle) / Resolution: 3.9 Å

72994

9yil

EMDB-72994, PDB-9yil:
HIV-1 Env del8-3fill SOSIP
Method: EM (single particle) / Resolution: 5.0 Å

Chemicals

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

Source
  • human immunodeficiency virus 1
  • macaca mulatta (Rhesus monkey)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 / Envelope protein / Vaccine / Immunogen / Antibody / bNAb / Viral Protein / VIRAL PROTEIN-IMMUNE SYSTEM complex

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