ArticleScience immunology2026
Env-antibody coevolution identifies B cell priming as the principal bottleneck to HIV V2 apex broadly neutralizing antibody development.
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Article in Science immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16citing papers in PubMed
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Who cites it
16 citing papers in PubMed.
- 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 · 2026Article
- Article
- Scientific synergy between prophylactic and therapeutic HIV vaccines-prevention and cure.NPJ vaccines · 2026Article
- Induction of broadly neutralizing HIV antibodies by a two-step mechanism informs vaccine design.Science (New York, N.Y.) · 2026Article
- 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
- Germline-targeting HIV immunogen induces cross-neutralizing antibodies in outbred macaques.Immunity · 2026Article
- Contemporary HIV-1 envelope pseudovirus panels for detecting and assessing B cell lineages with broadly neutralizing antibody potential.PLoS pathogens · 2026Article
- Early clonal dominance at priming sets the trajectory for broad HIV serum neutralization.bioRxiv : the preprint server for biology · 2026Article
- Rapidly acquired HIV-1 neutralization breadth in a rhesus V2 apex knockin mouse model after a single bolus immunization.Science immunology · 2026Article
- Contemporary HIV-1 envelope pseudovirus panels for detecting and assessing B cell lineages with broadly neutralizing antibody potential.bioRxiv : the preprint server for biology · 2025Article
- Structure-guided design of native-like HIV Env Single Chain Trimers for enhanced stability, immunogenicity, and versatile vaccine delivery.bioRxiv : the preprint server for biology · 2025Article
- Germline-targeting HIV immunogen induces cross-neutralizing antibodies in outbred macaques.bioRxiv : the preprint server for biology · 2025Article
- Consistent Induction of Broadly Neutralizing HIV Antibodies by a Novel Two-Step Mechanism Informs Immunogen Design.bioRxiv : the preprint server for biology · 2025Article
- Structural and genetic basis of HIV-1 envelope V2 apex recognition by rhesus broadly neutralizing antibodies.The Journal of experimental medicine · 2025Article
- Transient glycan shield reduction induces CD4-binding site broadly neutralizing antibodies in SHIV-infected macaques.Cell reports · 2025Article
- Rapid acquisition of HIV-1 neutralization breadth in a rhesus V2 apex germline antibody mouse model after a single bolus immunization.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
51 authors.
Rumi HabibDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-2812-8263
Ryan S RoarkAaron Diamond AIDS Research Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.ORCID 0000-0003-0586-103X
Hui LiDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0001-7231-8219
Andrew Jesse ConnellDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-9393-3074
Michael P HogartyDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-3513-0222
Kshitij WaghDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Shuyi WangDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0009-0005-8791-0318
Lorie MarchittoDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ashwin N SkellyDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-1565-3376
John W CareyDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0009-0007-9261-3830
Kirsten J SowersDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0009-0005-7602-9461
Kasirajan AyyanathanDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0003-1643-4009
Samantha J PlanteDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0009-0001-4667-8031
Frederic Bibollet-RucheDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0009-0003-7518-6487
Younghoon ParkDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0009-0003-5069-504X
Colby J AgostinoVaccine and Immunotherapy Center, Wistar Institute, Philadelphia, PA 19104, USA.ORCID 0000-0002-1864-1848
Ajay SinghDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0001-7751-2934
Christian L MartellaDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0009-0004-7175-9185
Emily LewisDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0001-5721-0787
Juliette M RandoDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-1742-9255
Neha ChohanDepartments 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.
Wenge DingDepartments 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.
Chengyan ZhaoDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Weimin LiuDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0003-2903-2834
Yingying LiDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-0237-6824
Xuduo LiDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0009-0004-1155-142X
Bo LiangDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Rohan Roy ChowdhuryDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0003-3586-571X
Khaled AmerehDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Elizabeth Van ItallieDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.ORCID 0000-0002-0736-7345
Zizhang ShengAaron Diamond AIDS Research Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.ORCID 0000-0002-3253-3309
Amrit R GhoshDepartments of Microbiology and Immunology, Harvard Medical School, Cambridge, MA 02139, USA.ORCID 0000-0002-0692-4074
Katharine J BarDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-9773-0071
Wilton B WilliamsDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.ORCID 0000-0002-2970-7259
Kevin WieheDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.ORCID 0000-0001-9933-9618
Kevin O SaundersDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.ORCID 0000-0001-7399-7954
Robert J EdwardsDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.ORCID 0000-0003-4446-1194
Derek W CainDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.ORCID 0000-0002-5988-6729
Mark G LewisBioqual Inc., Rockville, MD 20850, USA.ORCID 0000-0001-7852-0135
Facundo D BatistaDepartments of Microbiology and Immunology, Harvard Medical School, Cambridge, MA 02139, USA.ORCID 0000-0002-1130-9463
Dennis R BurtonDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0001-6711-9864
Raiees AndrabiDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0001-8837-7520
Daniel W KulpVaccine and Immunotherapy Center, Wistar Institute, Philadelphia, PA 19104, USA.
Barton F HaynesDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.ORCID 0000-0002-7643-9023
Bette KorberNew Mexico Consortium, Los Alamos, NM 87545, USA.ORCID 0000-0002-2026-5757
Lawrence ShapiroAaron Diamond AIDS Research Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.ORCID 0000-0001-9943-8819
Peter D KwongAaron Diamond AIDS Research Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.ORCID 0000-0003-3560-232X
Beatrice H HahnDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-9400-9887
George M ShawDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-2338-4532
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 Ronald G Collman · 1999 to 2026
$78.6MVaccine and adjuvant Clinical GMP product development and DNA Technology platform enhancementsU19AI166916 · NIAID · WISTAR INSTITUTE · PI DAVID B. WEINER · 2023 to 2026
$24.0MTRAINING 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
$6.9MHIV-1 Q23.17 Env: Engineering a novel immunogen to elicit broadly neutralizing antibodiesR01AI165080 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI GEORGE M SHAW · 2021 to 2026
$6.6MANIMAL HUSBANDRY SUPPORT SERVICES FOR NIEHS27304C0002 · NIEHS · 2007 to 2008
$5.0MB 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
$4.7MNeonatal Immunity to novel TF SHIVsR01AI140897 · NIAID · DUKE UNIVERSITY · PI WILLIAMS, WILTON B · 2018 to 2022
$4.4MCombining 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
$3.2MBill & Melinda Gates Foundation INV-041767NIAID NIH HHS P30 AI045008NIAID NIH HHS R01 AI140897NIAID NIH HHS R01 AI160607NIAID NIH HHS R01 AI165080NIAID NIH HHS R01 AI167716NIAID NIH HHS R01 AI183332NIAID NIH HHS R33 AI161818NIAID NIH HHS R37 AI140897NIAID NIH HHS R37 AI150590NIAID NIH HHS R61 AI161818NIAID NIH HHS T32 AI007632NIAID NIH HHS U19 AI166916NIAID NIH HHS UM1 AI144371NIAID NIH HHS UM1 AI144462NIEHS NIH HHS 27304C0002NIEHS NIH HHS 27306C0002
Abstract
Broadly neutralizing antibodies (bNAbs) are rarely elicited during HIV-1 infection. To identify obstacles to bNAb development, we longitudinally studied 122 rhesus macaques infected by 1 of 16 different simian-human immunodeficiency viruses (SHIVs). We identified the V2 apex region of the envelope (Env) as the most common bNAb target and a subset of Envs that preferentially elicited these antibodies. In 10 macaques, we delineated Env-antibody coevolution from B cell priming to bNAb development. Antibody phylogenies revealed permissive developmental pathways guided by evolving Envs that contained few mutations in or near the V2 apex C-strand, which were a sensitive indicator of apex-targeted responses. The absence of such mutations reflected a failure in bNAb priming. These results indicate that efficiency of B cell priming, and not complexities in Env-guided affinity maturation, is a primary obstacle to V2 apex bNAb elicitation in SHIV-infected macaques and identify specific HIV-1 Envs to advance as vaccine platforms.
Indexed as
Antibodies, NeutralizingB-Lymphocytesenv Gene Products, Human Immunodeficiency VirusHIV-1HIV AntibodiesHIV InfectionsAnimalsHumansMacaca mulattaSimian Acquired Immunodeficiency SyndromeSimian Immunodeficiency VirusAntibodies, Neutralizingenv Gene Products, Human Immunodeficiency VirusHIV Antibodies
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