Evidence map›Paper›PMID 40824240›Full record

ArticleThe Journal of experimental medicine2025

Structural and genetic basis of HIV-1 envelope V2 apex recognition by rhesus broadly neutralizing antibodies.

Ryan S Roark, Rumi Habib, Jason Gorman, Hui Li, Andrew Jesse Connell, Mattia Bonsignori, Yicheng Guo, Michael P Hogarty, Adam S Olia, Kirsten J Sowers and 32 more

Abstract read
In one paragraph

Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed.

  1. Deletions in variable region 1 of the HIV envelope accelerate V3-glycan bNAb induction in SHIV-infected rhesus macaques.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Priming of Multiple HIV Neutralizing B Cell Precursors in Humans.medRxiv : the preprint server for health sciences · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

42 authors.

Ryan S Roark *Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons , New York, NY, USA.ORCID 0000-0003-0586-103X
Rumi Habib *Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-2812-8263
Jason GormanVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0002-3775-6560
Hui LiDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-7231-8219
Andrew Jesse ConnellDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-9393-3074
Mattia BonsignoriTranslational Immunobiology Unit, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0003-2973-2101
Yicheng GuoAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons , New York, NY, USA.ORCID 0000-0001-5357-660X
Michael P HogartyDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-3513-0222
Adam S OliaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0003-0805-1331
Kirsten J SowersDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0009-0005-7602-9461
Baoshan ZhangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0002-0165-1513
Frederic Bibollet-RucheDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0009-0003-7518-6487
Tatsiana BylundVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0002-2065-2773
Sean CallaghanDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0003-2966-994X
John W CareyDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0009-0007-9261-3830
Gabriele CeruttiDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.ORCID 0000-0002-9081-7561
Darcy R HarrisVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0002-3671-6452
Wanting HeDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0003-4692-3516
Emily LewisDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-5721-0787
Tracy LiuVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0009-0005-0346-3232
Rosemarie D MasonVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0001-7123-4902
Yujie QiaoAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons , New York, NY, USA.ORCID 0009-0009-7182-2355
Younghoon ParkDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0009-0003-5069-504X
Juliette M RandoDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-1742-9255
Ajay SinghDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-7751-2934
Jeremy J WolffVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0009-0000-6233-5357
Q Paula LeiVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0002-3656-4014
Mark K LouderVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.
Raiees AndrabiDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-8837-7520
Nicole A Doria-RoseVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0002-5731-3054
Kevin O SaundersDepartment of Integrative Immunobiology, Duke University School of Medicine, Durham, NC, USA.ORCID 0000-0001-7399-7954
Michael S SeamanCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center , Boston, MA, USA.ORCID 0000-0001-6444-3562
Barton F HaynesDepartment of Integrative Immunobiology, Duke University School of Medicine, Durham, NC, USA.ORCID 0000-0002-7643-9023
Daniel W KulpDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-0527-3804
John R MascolaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0002-5293-4695
Mario RoedererVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0001-7448-7040
Theodore C PiersonVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0002-3795-4348
Zizhang ShengAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons , New York, NY, USA.ORCID 0000-0002-3253-3309
Beatrice H HahnDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-9400-9887
George M ShawDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-2338-4532
Peter D KwongAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons , New York, NY, USA.ORCID 0000-0003-3560-232X
Lawrence ShapiroAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons , New York, NY, USA.ORCID 0000-0001-9943-8819

Funding

Nonhuman primate studies for development of a prototype HIV vaccine that induces broadly neutralizing antibodiesUM1AI144371 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F. · 2019 to 2025
$190.4M
Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Ronald G Collman · 1999 to 2026
$78.6M
TRAINING IN HIV PATHOGENESIST32AI007632 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Frederic D Bushman, James L. Riley · 2000 to 2026
$10.6M
Optimizing glycan shield coverage, germline B cell receptor binding and epitope diversity of V2-apex targeted HIV-1 Env immunogensR37AI150590 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Beatrice H Hahn · 2019 to 2026
$6.9M
HIV-1 Q23.17 Env: Engineering a novel immunogen to elicit broadly neutralizing antibodiesR01AI165080 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI GEORGE M SHAW · 2021 to 2026
$6.6M
Natural SIV Reservoirs and Human Zoonotic RiskR01AI050529 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HAHN, BEATRICE H · 2001 to 2022
$6.1M
B cell lineage-directed rational vaccine strategies based on CAP256SU Env-Ab co-evolutionR01AI167716 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Raiees Ahmad Andrabi · 2022 to 2026
$4.8M
Combining germline-targeting, B cell immunofocusing and Env-Ab coevolution strategies to induce HIV Envelope V2-apex broadly neutralizing antibodiesR61AI161818 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ANDRABI, RAIEES AHMAD, SHAW, GEORGE M · 2021 to 2023
$4.7M
Reverse Vaccinology in SHIV Infected Macaques as a Molecular Guide for HIV-1 Vaccine DesignR01AI160607 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI SHAW, GEORGE M · 2021 to 2024
$3.2M
Quick and Accurate Measurements of HIV Broadly Neutralizing Antibody SusceptibilityR61AI176583 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SHENG, ZIZHANG, WU, XUELING · 2023 to 2025
$3.0M
Duke Consortium for HIV Vaccine Development UM1 AI 144371Duke Human Vaccine InstituteGates Foundation INV-007939Gates Foundation INV-041767National Institute of Allergy and Infectious DiseasesNHLBI NIH HHSNIAID NIH HHS P30 AI045008NIAID NIH HHS R01 AI050529NIAID NIH HHS R01 AI160607NIAID NIH HHS R01 AI165080NIAID NIH HHS R01 AI167716NIAID NIH HHS R37 AI150590NIAID NIH HHS R61 AI161818NIAID NIH HHS R61 AI176583NIAID NIH HHS T32 AI007632NIAID NIH HHS UM1 AI144371NIH HHS R01 AI 050529NIH HHS R01 AI160607NIH HHS R01 AI165080NIH HHS R01 AI 167716NIH HHS R37 AI 150590NIH HHS R61 AI 161818NIH HHS R61 AI 176583Training Grant in HIV Pathogenesis T32-AI007632Vaccine Research Center
6 · The paper itself

Abstract

Broadly neutralizing antibodies targeting the V2 apex of HIV-1 envelope are desired as vaccine design templates, but few have been described. Here, we report 11 lineages of V2 apex-neutralizing antibodies from simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and determine cryo-EM structures for 9. A single V2 apex-neutralizing lineage accounted for cross-clade breadth in most macaques, and somatic hypermutation relative to breadth was generally low, exemplified by antibody V033-a.01 with <5% nucleotide mutation and 37% breadth (208-strain panel). Envelope complex structures revealed eight different antibody classes (one multi-donor) and the complete repertoire of all five possible recognition topologies, recapitulating canonical human modes of apex insertion and C-strand hydrogen bonding. Despite this diversity in recognition, all rhesus-V2 apex antibodies were derived from reading frame two of the DH3-15*01 gene. Collectively, these results define-in rhesus-the structural and genetic basis of HIV-1 V2 apex recognition and demonstrate unprecedented structural plasticity of a highly selected immunogenetic element.

Indexed as

Antibodies, Neutralizingenv Gene Products, Human Immunodeficiency VirusHIV-1HIV AntibodiesAnimalsCryoelectron MicroscopyHumansMacaca mulattaModels, MolecularSimian Immunodeficiency VirusAntibodies, Neutralizingenv Gene Products, Human Immunodeficiency VirusHIV Antibodies

Identifiers

PMID40824240
PMCPMC12379892

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.