Evidence map›Paper›PMID 41279569›Full record

ArticlebioRxiv : the preprint server for biology2025

Germline-targeting HIV immunogen induces cross-neutralizing antibodies in outbred macaques.

Nitesh Mishra, Bo Liang, Ryan S Roark, Amrit Ghosh, Sean Callaghan, Wen-Hsin Lee, Xuduo Li, Anh L Vo, Gabriel Avillion, Rohan Roy Chowdhury and 42 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

52 authors.

Nitesh MishraDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Bo LiangDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ryan S RoarkAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
Amrit GhoshRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02114, USA.
Sean CallaghanDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Wen-Hsin LeeDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 28 92037, USA.
Xuduo LiDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Anh L VoDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Gabriel AvillionDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Rohan Roy ChowdhuryDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Rumi H HabibDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-2812-8263
Frederic Bibollet-RucheDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Gabriella GieseDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Prabhgun OberoiDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Khaled AmerehDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Anjali SomanathanDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Yuxin ZhuDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Yuexiu ZhangDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Muzaffer KassabDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Lifei TjioDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Sharaf AndrabiDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Raphael A ReyesRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02114, USA.ORCID 0000-0002-2234-4758
Joel D AllenSchool of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.ORCID 0000-0003-2547-968X
Nicole E JamesSchool of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.
Kipchoge N RandallDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 28 92037, USA.
Lara van der MaasDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 28 92037, USA.
Elana Ben-AkivaKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Kasia Kacmarek-MichaelsKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Samantha PlanteDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Christian L MartellaDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ashwin N SkellyDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ajay SinghDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jonathan HurtadoDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Katharina DuekerDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Tazio CapozzolaDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Rebecca NedellecDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Gabriel OzorowskiDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 28 92037, USA.
Mark M LewisBioqual, Inc., Rockville, Maryland, USA.
Samantha FalconeModerna, Inc., Cambridge, Ma 02139, USA.
Andrea CarfiModerna, Inc., Cambridge, Ma 02139, USA.
Sunny HimansuModerna, Inc., Cambridge, Ma 02139, USA.
Lawrence ShapiroDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10027, USA.
Max CrispinSchool of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.ORCID 0000-0002-1072-2694
Beatrice H HahnDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Bryan BrineyDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Darrell J IrvineDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Dennis R BurtonDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Andrew B WardConsortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0001-7153-3769
Facundo D BatistaConsortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Peter D KwongAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
George M ShawDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Raiees AndrabiDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Funding

Identification of neutralizing epitopes on SARS-CoV-2 spike for design of vaccines and small-molecule antiviralsUM1AI144462 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2019 to 2025
$201.6M
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
The Multi-omics Vaccine Evaluation (MOVE) ConsortiumP01AI177683 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI Laura D. Hughes · 2023 to 2026
$9.0M
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
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
Gates Foundation INV-041767NIAID NIH HHS P01 AI177683NIAID NIH HHS P30 AI045008NIAID NIH HHS R01 AI160607NIAID NIH HHS R01 AI165080NIAID NIH HHS R01 AI167716NIAID NIH HHS R37 AI150590NIAID NIH HHS R61 AI161818NIAID NIH HHS UM1 AI144371NIAID NIH HHS UM1 AI144462
6 · The paper itself

Abstract

Germline-targeting-(GT) is a promising strategy to activate rare broadly neutralizing antibody (bnAb)-producing B cells against HIV, but induction of such responses in outbred animals has not been achieved. Using antibody-guided structure-based design, we engineered a germline-targeting trimer immunogen Q23-APEX-GT2 that primes diverse V2-apex bnAb precursors. Q23-APEX-GT2 efficiently activated V2-apex-specific B cells in humanized knock-in mice and consistently elicited immunofocused antibody responses in rhesus macaques, priming multiple long CDRH3-loop bnAb-B cell lineages. Monoclonal antibodies from immunized macaques exhibited broad heterologous HIV trimer binding and cross-neutralization. Atomic-level structural studies confirmed precise epitope targeting and revealed CDRH3-paratope configurations that mirrored those of human V2-apex bnAbs. This study provides proof-of-principle for successful priming and maturation of authentic V2-apex bnAb precursors in outbred macaques, underscoring the potential of V2-apex-targeted vaccines.

Identifiers

PMID41279569
PMCPMC12633350

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.