ArticleScience immunology2024
Germline-targeting HIV vaccination induces neutralizing antibodies to the CD4 binding site.
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Article in Science immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39citing papers in PubMed
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Who cites it
39 citing papers in PubMed.
- Precise targeting of HIV broadly neutralizing antibody precursors in humans.Science (New York, N.Y.) · 2025Trial
- 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
- Advances in Vaccines Against Infectious Diseases.Vaccines · 2026Article
- Overcoming immunogenic gaps in malaria subunit vaccines by broadening CSP regions targeted.The Journal of experimental medicine · 2026Article
- Learned young: HIV-1 germline-targeting vaccination in infants.Current opinion in HIV and AIDS · 2026Review
- Comparison of Systemic and Mucosal Synchronous Immunization with Replicating Single-cycle Adenoviruses and SOSIP Protein HIV-1 Vaccines.Research square · 2026Article
- Article
- HIV-1 BG505 SOSIP immunization induced B cell expansion targeting the 465-glycan hole, with neutralizing antibodies exhibiting distinct binding modes and mechanisms of virus inhibition.PLoS pathogens · 2026Article
- Maturation of HIV-1 neutralizing antibodies in a germinal center conditional expression mouse model.PLoS pathogens · 2026Article
- The evolution of display technologies for antibody drug discovery.Trends in biotechnology · 2026Review
- Safety and immunogenicity of an HIV envelope trimer immunogen that elicits CD4 binding site neutralizing antibody precursors (HVTN 300).medRxiv : the preprint server for health sciences · 2026Article
- Decoding the glycan shield: Immune recognition and response to the HIV-1 envelope trimer.The Journal of biological chemistry · 2026Review
- Recurrent SARS-CoV-2 Omicron broadly neutralizing humanized antibodies in different single human VProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Decoding epitope immunodominance in HIV Env using cryoEM and machine learning.bioRxiv : the preprint server for biology · 2026Article
- Epitope-spanning antigenic variation reprograms immunodominance and broadens immunity in sequential influenza vaccination.Nature communications · 2026Article
- Rapid elicitation of neutralizing Asn332-glycan-independent antibodies to the V3-glycan epitope of HIV-1 Env in nonhuman primates.Nature immunology · 2026Article
- Nanoparticle Immunoadjuvant Complexes Augment Germinal Center Responses to Vaccination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Functional Convergence of Genetically Diverse B-Cell Receptors in Simian-HIV Infected Rhesus Macaques.bioRxiv : the preprint server for biology · 2026Article
- Unveiling an Immunological Mystery: Deciphering the Durability Divide in Vaccine-Elicited Antibody Responses.Current HIV research · 2026Review
- Accelerating Innovation: Advancing Opportunities in HIV Vaccine Development.Current HIV research · 2026Review
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Authors and funding
48 authors.
Tom G CanielsAmsterdam UMC, location AMC, University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Amsterdam, Netherlands.ORCID 0000-0001-9580-157X
Max Medina-RamìrezAmsterdam UMC, location AMC, University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Amsterdam, Netherlands.ORCID 0000-0001-6520-3501
Shiyu ZhangDepartment of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0003-4586-0605
Sven KratochvilRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA, USA.ORCID 0000-0002-0446-2371
Yuejiao XianDepartment of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA, USA.
Ja-Hyun KooRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA, USA.ORCID 0000-0002-0291-6288
Ronald DerkingAmsterdam UMC, location AMC, University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Amsterdam, Netherlands.
Jakob SamselVaccine Research Center (VRC), NIAID, NIH, Bethesda, MD, USA.ORCID 0000-0003-4026-5575
Jelle van SchootenAmsterdam UMC, location AMC, University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Amsterdam, Netherlands.ORCID 0000-0002-5202-355X
Simone PecettaRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA, USA.ORCID 0000-0001-9898-4324
Edward LampertiRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA, USA.ORCID 0009-0004-9328-6411
Meng YuanDepartment of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0001-9754-4503
María Ríos CarrascoAmsterdam UMC, location AMC, University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Amsterdam, Netherlands.ORCID 0000-0001-7000-2018
Iván Del Moral SánchezAmsterdam UMC, location AMC, University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Amsterdam, Netherlands.ORCID 0000-0002-6356-1484
Joel D AllenSchool of Biological Sciences, University of Southampton, Southampton, UK.ORCID 0000-0003-2547-968X
Joey H BouhuijsAmsterdam UMC, location AMC, University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Amsterdam, Netherlands.ORCID 0000-0002-6074-8542
Anila YasmeenDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA.ORCID 0000-0002-2386-8991
Thomas J KetasDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA.ORCID 0000-0001-9380-7716
Jonne L SnitselaarAmsterdam UMC, location AMC, University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Amsterdam, Netherlands.ORCID 0000-0002-2425-8335
Tom P L BijlAmsterdam UMC, location AMC, University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Amsterdam, Netherlands.
Isabel Cuella MartinAmsterdam UMC, location AMC, University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Amsterdam, Netherlands.ORCID 0000-0001-7543-3386
Jonathan L TorresDepartment of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0003-0137-8497
Albert CupoDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA.ORCID 0000-0001-7579-3525
Lisa ShirreffNew Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA.ORCID 0000-0002-8403-451X
Kenneth RogersNew Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA.ORCID 0000-0002-3911-035X
Rosemarie D MasonVaccine Research Center (VRC), NIAID, NIH, Bethesda, MD, USA.ORCID 0000-0001-7123-4902
Mario RoedererVaccine Research Center (VRC), NIAID, NIH, Bethesda, MD, USA.ORCID 0000-0001-7448-7040
Kelli M GreeneDuke University Medical Center, Durham, NC, USA.
Hongmei GaoDuke University Medical Center, Durham, NC, USA.ORCID 0000-0002-2468-8589
Catarina Mendes SilvaAmsterdam UMC, location AMC, University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Amsterdam, Netherlands.ORCID 0009-0007-3419-2513
Isabel J L BakenAmsterdam UMC, location AMC, University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Amsterdam, Netherlands.ORCID 0009-0006-6818-1401
Ming TianHoward Hughes Medical Institute, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-4350-3380
Frederick W AltHoward Hughes Medical Institute, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-0583-1271
Bali PulendranInstitute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.ORCID 0000-0001-6517-4333
Michael S SeamanCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.ORCID 0000-0001-6444-3562
Max CrispinSchool of Biological Sciences, University of Southampton, Southampton, UK.ORCID 0000-0002-1072-2694
Marit J van GilsAmsterdam UMC, location AMC, University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Amsterdam, Netherlands.ORCID 0000-0003-3422-8161
David C MontefioriDuke University Medical Center, Durham, NC, USA.ORCID 0000-0003-0856-6319
Adrian B McDermottVaccine Research Center (VRC), NIAID, NIH, Bethesda, MD, USA.ORCID 0000-0003-0616-9117
François J VillingerNew Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA.ORCID 0000-0002-7790-2008
Richard A KoupVaccine Research Center (VRC), NIAID, NIH, Bethesda, MD, USA.ORCID 0000-0002-3090-7282
John P MooreDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA.ORCID 0000-0002-9902-6096
Per Johan KlasseDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA.ORCID 0000-0001-8222-278X
Gabriel OzorowskiDepartment of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0002-9695-8138
Facundo D BatistaDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID 0000-0002-1130-9463
Ian A WilsonDepartment of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0002-6469-2419
Andrew B WardDepartment of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0001-7153-3769
Rogier W SandersAmsterdam UMC, location AMC, University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Amsterdam, Netherlands.ORCID 0000-0002-2324-8573
Funding
A Synchrotron Radiation Structural Biology ResourcesP30GM133894 · NIGMS · STANFORD UNIVERSITY · PI Ritimukta Sarangi · 2020 to 2026
$43.3MStructural studies of native-like SOSIP trimersP01AI110657 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOORE, JOHN P · 2015 to 2024
$35.4MUser Training & OutreachP30GM138396 · NIGMS · UCHICAGO ARGONNE, LLC · PI ROBERT F. FISCHETTI, JANET L. SMITH · 2020 to 2026
$34.3MSystems biological assessment of T cell responses to vaccinationU19AI167903 · NIAID · STANFORD UNIVERSITY · PI BALI PULENDRAN · 2022 to 2026
$13.2MMonoclonal antibody isolation and characterizationZIAAI005126 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MASON, ROSEMARIE · 2015 to 2025
$10.1MNeutralization of Primate Immunodeficiency VirusesR01AI036082 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI JOHN P MOORE · 1994 to 2026
$4.3MGates Foundation INV-002022Gates Foundation INV-002916Gates Foundation INV-007368Gates Foundation INV-008352Gates Foundation INV-009585Gates Foundation INV-036842NIAID NIH HHS P01 AI110657NIAID NIH HHS R01 AI036082NIAID NIH HHS U19 AI167903NIGMS NIH HHS P30 GM133894NIGMS NIH HHS P30 GM138396
Abstract
Eliciting potent and broadly neutralizing antibodies (bnAbs) is a major goal in HIV-1 vaccine development. Here, we describe how germline-targeting immunogen BG505 SOSIP germline trimer 1.1 (GT1.1), generated through structure-based design, engages a diverse range of VRC01-class bnAb precursors. A single immunization with GT1.1 expands CD4 binding site (CD4bs)-specific VRC01-class B cells in knock-in mice and drives VRC01-class maturation. In nonhuman primates (NHPs), GT1.1 primes CD4bs-specific neutralizing serum responses. Selected monoclonal antibodies (mAbs) isolated from GT1.1-immunized NHPs neutralize fully glycosylated BG505 virus. Two mAbs, 12C11 and 21N13, neutralize subsets of diverse heterologous neutralization-resistant viruses. High-resolution structures revealed that 21N13 targets the same conserved residues in the CD4bs as VRC01-class and CH235-class bnAbs despite its low sequence similarity (~40%), whereas mAb 12C11 binds predominantly through its heavy chain complementarity-determining region 3. These preclinical data underpin the ongoing evaluation of GT1.1 in a phase 1 clinical trial in healthy volunteers.
Indexed as
AIDS VaccinesAntibodies, NeutralizingCD4 AntigensHIV-1HIV AntibodiesAnimalsAntibodies, MonoclonalBinding SitesFemaleHIV InfectionsHumansMiceVaccinationAIDS VaccinesAntibodies, MonoclonalAntibodies, NeutralizingCD4 AntigensHIV Antibodies
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