Evidence map›Paper›PMID 40516049›Full record

ArticleCell reports2025

Transient glycan shield reduction induces CD4-binding site broadly neutralizing antibodies in SHIV-infected macaques.

Daniel J Morris, Jason Gorman, Tongqing Zhou, Jinery Lora, Andrew J Connell, Hui Li, Weimin Liu, Ryan S Roark, Mary S Campion, John W Carey and 26 more

Abstract read
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 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
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  6. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

36 authors.

Daniel J MorrisDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jason GormanVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Tongqing ZhouVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Jinery LoraDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Andrew J ConnellDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Hui LiDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Weimin LiuDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ryan S RoarkAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
Mary S CampionDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
John W CareyDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Rumi HabibDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA.
Yingying LiDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Christian L MartellaDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Younghoon ParkDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ajay SinghDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kirsten J SowersDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
I-Ting TengVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Shuyi WangDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Neha ChohanDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Wenge DingDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Craig LauerDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Emily LewisDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Rosemarie D MasonVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Juliette M RandoDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Lowrey PeytonVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Chaim A SchrammVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Kshitij WaghDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
Bette KorberNew Mexico Consortium, Los Alamos, NM, USA.
Michael S SeamanCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Daniel C DouekVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Barton F HaynesDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA; Departments of Immunology and Medicine, Duke University School of Medicine, Durham, NC, USA.
Daniel W KulpVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA.
Mario RoedererVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Beatrice H HahnDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Peter D KwongVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. Electronic address: pdk3@cumc.columbia.edu.
George M ShawDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: shawg@pennmedicine.upenn.edu.

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
Stuctural basis of bNab activityP01AI100148 · NIAID · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI Pamela J Bjorkman · 2013 to 2026
$43.3M
Vaccine and adjuvant Clinical GMP product development and DNA Technology platform enhancementsU19AI166916 · NIAID · WISTAR INSTITUTE · PI DAVID B. WEINER · 2023 to 2026
$24.0M
TRD #3: An automated and streamlined pipeline for in-situ molecular microscopyP41GM103310 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI DE MARCO, ALEX, KIEFT, JEFFREY S · 2012 to 2021
$14.7M
TRAINING IN HIV PATHOGENESIST32AI007632 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Frederic D Bushman, James L. Riley · 2000 to 2026
$10.6M
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
NIAID NIH HHS P01 AI100148NIAID NIH HHS P30 AI045008NIAID NIH HHS R01 AI160607NIAID NIH HHS T32 AI007632NIAID NIH HHS U19 AI166916NIAID NIH HHS UM1 AI144371NIGMS NIH HHS P41 GM103310
6 · The paper itself

Abstract

Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 CD4-binding site (CD4bs) occur infrequently in macaques and humans and have not been reproducibly elicited in any outbred animal model. To address this challenge, we first isolated RHA10, an infection-induced rhesus bNAb with 51% breadth. The cryoelectron microscopy (cryo-EM) structure of RHA10 with the HIV-1 envelope (Env) resembled prototypic human CD4bs bNAbs with CDR-H3-dominated binding. Env-antibody co-evolution revealed transient elimination of two Env CD4bs-proximal glycans near the time of RHA10-lineage initiation, and these glycan-deficient Envs bound preferentially to early RHA10 intermediates, suggesting that glycan deletions in infecting SHIVs could induce CD4bs bNAbs. To test this hypothesis, we constructed SHIV.CH505 variants with CD4bs-proximal glycan deletions. Infection of 11 macaques resulted in accelerated CD4bs bNAb responses in 9 compared with 1 of 115 control macaques. Glycan hole-based immunofocusing coupled to Env-Ab co-evolution can consistently induce broad CD4bs responses in macaques and serve as a model for HIV vaccine design.

Indexed as

Antibodies, NeutralizingBroadly Neutralizing AntibodiesCD4 AntigensHIV-1HIV AntibodiesPolysaccharidesSimian Acquired Immunodeficiency SyndromeSimian Immunodeficiency VirusAnimalsBinding SitesHumansMacaca mulattaAntibodies, NeutralizingBroadly Neutralizing AntibodiesCD4 AntigensHIV AntibodiesPolysaccharidesbroadly neutralizing antibodyCD4-binding siteco-evolutionCP: Immunologyglycan deletionHIV-1simian-human immunodeficiency virus (SHIV)structure-guided vaccine design

Identifiers

PMID40516049
PMCPMC12269249

What OpenQuestion holds

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Registered trials

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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.