ArticleImmunity2026
Germline-targeting HIV immunogen induces cross-neutralizing antibodies in outbred macaques.
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Article in Immunity, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Article
- Article
- Deep mining of the human antibody repertoire identifies frequent and genetically diverse CDRH3 topologies targetable by vaccination.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Ageing tissue fibroblasts support lung inflammaging.Nature reviews. Immunology · 2026Article
- Early clonal dominance at priming sets the trajectory for broad HIV serum neutralization.bioRxiv : the preprint server for biology · 2026Article
- The buried S2 apex of SARS-CoV-2 spike elicits an immunodominant germline-restricted public antibody response.bioRxiv : the preprint server for biology · 2026Article
- Env-antibody coevolution identifies B cell priming as the principal bottleneck to HIV V2 apex broadly neutralizing antibody development.Science immunology · 2026Article
- Rapidly acquired HIV-1 neutralization breadth in a rhesus V2 apex knockin mouse model after a single bolus immunization.Science immunology · 2026Article
Corrections and comments
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Authors and funding
52 authors.
Nitesh MishraDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), 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; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10027, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
Amrit Raj GhoshRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Department of Immunology, Harvard Medical School, Harvard University, Cambridge, MA 02114, USA.
Sean CallaghanDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), 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 92037, USA.
Xuduo LiDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, 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; Department of Microbiology, 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; Consortium for HIV/AIDS Vaccine Development (CHAVD), 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; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Rumi HabibDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Frederic Bibollet-RucheDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, 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; Department of Microbiology, 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; Department of Microbiology, 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; Department of Microbiology, 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; Department of Microbiology, 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; Department of Microbiology, 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; Department of Microbiology, 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; Department of Microbiology, 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; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Raphael A ReyesRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Department of Immunology, Harvard Medical School, Harvard University, Cambridge, MA 02114, USA.
Joel D AllenSchool of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.
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 92037, USA.
Lara van der MaasDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Elana Ben-AkivaKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Kasia Kacmarek-MichaelsKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Samantha PlanteDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, 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; Department of Microbiology, 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; Department of Microbiology, 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; Department of Microbiology, 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; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Katharina DuekerDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Tazio CapozzolaDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Rebecca NedellecDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, 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 92037, USA.
Mark G LewisBioqual, Inc., Rockville, MD, 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; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
Max CrispinSchool of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.
Beatrice H HahnDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, 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; Consortium for HIV/AIDS Vaccine Development (CHAVD), 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; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Dennis R BurtonDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Department of Immunology, Harvard Medical School, Harvard University, Cambridge, MA 02114, USA; IAVI Neutralizing Antibody Center, 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; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Facundo D BatistaRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Department of Immunology, Harvard Medical School, Harvard University, Cambridge, MA 02114, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: fbatista1@mgh.harvard.edu.
Peter D KwongAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10027, USA. Electronic address: pdk3@cumc.columbia.edu.
George M ShawDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: shawg@pennmedicine.upenn.edu.
Raiees AndrabiDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: raiees.andrabi@pennmedicine.upenn.edu.
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
$201.6MNonhuman primate studies for development of a prototype HIV vaccine that induces broadly neutralizing antibodiesUM1AI144371 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F. · 2019 to 2025
$190.4MVirus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Alisa Jane Stephens Shields · 1999 to 2026
$78.6MThe Multi-omics Vaccine Evaluation (MOVE) ConsortiumP01AI177683 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI Bryan Briney · 2023 to 2026
$9.0MOptimizing 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
$6.9MHIV-1 Q23.17 Env: Engineering a novel immunogen to elicit broadly neutralizing antibodiesR01AI165080 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI GEORGE M SHAW · 2021 to 2026
$6.6MB cell lineage-directed rational vaccine strategies based on CAP256SU Env-Ab co-evolutionR01AI167716 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Raiees Ahmad Andrabi · 2022 to 2026
$4.8MCombining 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
$4.7MCombining germline-targeting, B cell immunofocusing and Env-Ab coevolution strategies to induce HIV Envelope V2-apex broadly neutralizing antibodiesR33AI161818 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ANDRABI, RAIEES AHMAD, SHAW, GEORGE M · 2024 to 2025
$3.2MReverse 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
$3.2MEngineering durable immunity by optimizing HIV vaccine parameters to drive long-lived plasma cell developmentR01AI192456 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI Bryan Briney · 2025 to 2026
$2.8MGates 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 R01 AI192456NIAID NIH HHS R33 AI161818NIAID NIH HHS R37 AI150590NIAID NIH HHS R61 AI161818NIAID NIH HHS UM1 AI144371NIAID NIH HHS UM1 AI144462
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 GT HIV trimer immunogen, Q23-APEX-GT2, which primes diverse V2-apex bnAb precursors. Q23-APEX-GT2 efficiently activated rare V2-apex-specific B cells in humanized knockin mice and consistently elicited immunofocused antibody responses in outbred rhesus macaques, priming multiple long heavy-chain complementarity-determining region 3 (CDRH3)-loop bnAb-B cell lineages. Monoclonal antibodies isolated from immunized macaques showed broad heterologous HIV trimer recognition and modest cross-neutralization of diverse tier-2 viruses. Cryoelectron microscopy (cryo-EM) structural studies confirmed precise epitope targeting and revealed CDRH3-mediated binding modes that mirrored those of human V2-apex bnAbs. Together, these findings establish proof of principle for priming and early maturation of authentic V2-apex bnAb precursors in outbred macaques and highlight the promise of V2-apex-targeted HIV vaccines.
Indexed as
AIDS VaccinesAntibodies, NeutralizingHIV-1HIV AntibodiesHIV InfectionsAnimalsAntibodies, MonoclonalB-LymphocytesComplementarity Determining RegionsCross ReactionsEpitopesGerm CellsHumansMacaca mulattaMiceAIDS VaccinesAntibodies, MonoclonalAntibodies, NeutralizingComplementarity Determining RegionsEpitopesHIV Antibodiesbroadly neutralizing antibodiescryo-EM structureenvelope trimergermline targetingHIV-1long CDRH3 antibodiesQ23-APEX-GT2tier 2 HIV neutralizationV2-apex bnAb epitopevaccines
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