ArticlebioRxiv : the preprint server for biology2025
Consistent Induction of Broadly Neutralizing HIV Antibodies by a Novel Two-Step Mechanism Informs Immunogen Design.
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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.
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57 authors.
Ashwin N SkellyDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Harry B GristickDivision of Biology and Biological Engineering, California Institute of Technology; Pasadena, CA 91125, USA.
Hui LiDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Edem GavorDivision of Biology and Biological Engineering, California Institute of Technology; Pasadena, CA 91125, USA.
Andrew J ConnellDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Edward F KreiderDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Lorie MarchittoDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Michael P HogartyDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Maddy L NewbySchool of Biological Sciences, University of Southampton; Southampton SO17 1BJ, UK.
Joel D AllenSchool of Biological Sciences, University of Southampton; Southampton SO17 1BJ, UK.
Weimin LiuDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Anthony P WestDivision of Biology and Biological Engineering, California Institute of Technology; Pasadena, CA 91125, USA.
Kasirajan AyyanathanDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Mary S CampionDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Kaitlyn WintersDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Colette G GordonDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Rebecca A OsbaldestonDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Macy J AkeleyDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Yingying LiDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Ajay SinghDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Kendra CruickshankDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Younghoon ParkDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Chengyan ZhaoDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Xuduo LiDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Khaled AmerehDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Elizabeth Van ItallieDuke Human Vaccine Institute and Department of Medicine, Duke University School of Medicine; Durham, NC 27710, USA.
John W CareyDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Amie AlbertusPenn Institute for RNA Innovation, Perelman School of Medicine, University of Pennsylvania, Philadelphia; PA 19104, USA.
Andrew T DeLaitschDivision of Biology and Biological Engineering, California Institute of Technology; Pasadena, CA 91125, USA.
Jennifer R KeeffeDivision of Biology and Biological Engineering, California Institute of Technology; Pasadena, CA 91125, USA.
Melinda G LituchyDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Agnes A WalshDepartment of Immunology and Microbiology, Scripps Research Institute; La Jolla, CA 92037, USA.
Daniel J MorrisDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Rumi HabibDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Frederic Bibollet-RucheDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Nitesh MishraDepartment of Immunology and Microbiology, Scripps Research Institute; La Jolla, CA 92037, USA.
Gabriel AvillionDepartment of Immunology and Microbiology, Scripps Research Institute; La Jolla, CA 92037, USA.
Nicholas S KorandaDivision of Biology and Biological Engineering, California Institute of Technology; Pasadena, CA 91125, USA.
Samantha J PlanteDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Christian L MartellaDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Jinery LoraDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Eric J D WangDivision of Biology and Biological Engineering, California Institute of Technology; Pasadena, CA 91125, USA.
Mark G LewisBioqual, Inc.; Rockville, MD 20850, USA.
Malcolm A MartinLaboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, MD 20892, USA.
Michel C NussenzweigLaboratory of Molecular Immunology, Rockefeller University; New York, NY 10065, USA.
Michael S SeamanCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center; Boston, MA 02215, USA.
Darrell J IrvineDepartment of Immunology and Microbiology, Scripps Research Institute; La Jolla, CA 92037, USA.
Kevin J WieheDuke Human Vaccine Institute and Department of Medicine, Duke University School of Medicine; Durham, NC 27710, USA.
Barton F HaynesDuke Human Vaccine Institute and Department of Medicine, Duke University School of Medicine; Durham, NC 27710, USA.
Kshitij WaghDuke Human Vaccine Institute and Department of Medicine, Duke University School of Medicine; Durham, NC 27710, USA.
Bette T KorberLos Alamos National Laboratory; Los Alamos, NM 87545, USA.
Raiees AndrabiDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Max CrispinSchool of Biological Sciences, University of Southampton; Southampton SO17 1BJ, UK.
Drew WeissmanPenn Institute for RNA Innovation, Perelman School of Medicine, University of Pennsylvania, Philadelphia; PA 19104, USA.
Pamela J BjorkmanDivision of Biology and Biological Engineering, California Institute of Technology; Pasadena, CA 91125, USA.
Beatrice H HahnDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
George M ShawDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
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
$190.4MMEDICAL SCIENTIST TRAINING PROGRAMT32GM007170 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BRASS, LAWRENCE F · 1985 to 2022
$54.0MStuctural basis of bNab activityP01AI100148 · NIAID · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI Pamela J Bjorkman · 2013 to 2026
$43.3MVirus and Antibody Gene Sequencing CoreP01AI131251 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Kevin Wiehe · 2017 to 2026
$40.7MTRAINING IN HIV PATHOGENESIST32AI007632 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Frederic D Bushman, James L. Riley · 2000 to 2026
$10.6MOptimizing 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
$6.9MReverse 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
$3.2MSHIV-infected rhesus macaques as a model for HIV-1 bNAb developmentR01AI197997 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI GEORGE M SHAW · 2026 to 2026
$804kHarnessing SHIVs and Sequential Immunization to Elicit V3 Glycan-Targeted bNAbs against HIV-1F30AI179430 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI SKELLY, ASHWIN NICHOLAS · 2024 to 2024
$37kGates Foundation INV-002143Gates Foundation INV-036842NIAID NIH HHS F30 AI179430NIAID NIH HHS P01 AI100148NIAID NIH HHS P01 AI131251NIAID NIH HHS R01 AI160607NIAID NIH HHS R01 AI197997NIAID NIH HHS R37 AI150590NIAID NIH HHS T32 AI007632NIAID NIH HHS UM1 AI144371NIGMS NIH HHS T32 GM007170
Abstract
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 novel 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.
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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.