ArticleCell reports. Medicine2023
Germline-targeting HIV-1 Env vaccination induces VRC01-class antibodies with rare insertions.
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Article in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41citing papers in PubMed
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Who cites it
41 citing papers in PubMed, 47 citations in OpenAlex.
- Precise targeting of HIV broadly neutralizing antibody precursors in humans.Science (New York, N.Y.) · 2025Trial
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- 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
- Article
- Article
- Rapid boosting increases germinal center responses to sequential vaccines.Nature immunology · 2026Article
- The sooner you boost the better.Nature immunology · 2026Article
- VRC01-CLASS PRECURSOR FREQUENCY IN AN AFRICAN POPULATION IS INFLUENCED BY IGHV1-2 ALLELIC COMPOSITION AND NOT MALARIA EXPOSURE.Research square · 2026Article
- Maturation of HIV-1 neutralizing antibodies in a germinal center conditional expression mouse model.PLoS pathogens · 2026Article
- High affinity is insufficient for strong B cell activation by HIV broadly neutralising antibodies.NPJ vaccines · 2026Article
- How Vaccinating People Living With HIV May Guide bNAb‑Based Vaccines.Journal of the International AIDS Society · 2026Article
- Contemporary HIV-1 envelope pseudovirus panels for detecting and assessing B cell lineages with broadly neutralizing antibody potential.PLoS pathogens · 2026Article
- Computing the inducibility of broadly neutralizing antibodies under a context-dependent model of affinity maturation: applications to sequential vaccine design.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Divalent HIV-1 gp120 Immunogen Exhibits Selective Avidity for Broadly Neutralizing Antibody VRC01 Precursors.Vaccines · 2026Article
- Germline-Targeting Strategies to Induce bNAbs against HIV-1.Current HIV research · 2026Review
- Current Approaches for Assessments of Neutralizing, Binding, and Effector Functions of Antibodies on the Path to Antibody-Mediated Prevention Strategies for HIV-1.Current HIV research · 2026Review
- The Germline Targeting Vaccine Concept: Overview and Updates from HIV Pre-Clinical and Clinical Trials.Current HIV research · 2026Review
- Integration of Preclinical and Clinical Vaccine Safety and Immunogenicity Testing for Development of a Pediatric HIV Vaccine to Achieve Protective HIV Immunity Prior to Adolescence.Current HIV research · 2026Review
- Accelerating Innovation: Advancing Opportunities in HIV Vaccine Development.Current HIV research · 2026Review
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Authors and funding
38 authors at 7 institutions in 4 countries.
Tom G CanielsDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands.
Max Medina-RamírezDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands.
Jinsong ZhangApplied Biomedical Science Institute, San Diego, CA, USA.
Anita SarkarDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Sonu KumarDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Alex LaBrancheApplied Biomedical Science Institute, San Diego, CA, USA.
Ronald DerkingDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands.
Joel D AllenSchool of Biological Sciences, University of Southampton, Southampton, UK.
Jonne L SnitselaarDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands.
Joan Capella-PujolDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands.
Iván Del Moral SánchezDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands.
Anila YasmeenDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA.
Marilyn DiazApplied Biomedical Science Institute, San Diego, CA, USA.
Yoann AldonDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands.
Tom P L BijlDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands.
Sravani VenkatayogiDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Joshua S Martin BeemDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Amanda NewmanDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Chuancang JiangDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA.
Wen-Hsin LeeDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Maarten PaterDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands.
Judith A BurgerDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands.
Mariëlle J van BreemenDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands.
Steven W de TaeyeDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands.
Kimmo RantalainenDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Celia LaBrancheDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Kevin O SaundersDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
David MontefioriDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
Gabriel OzorowskiDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Max CrispinSchool of Biological Sciences, University of Southampton, Southampton, UK.
John P MooreDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA.
Per Johan KlasseDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA.
Barton F HaynesDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
Ian A WilsonDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA.
Kevin WieheDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
Laurent VerkoczyApplied Biomedical Science Institute, San Diego, CA, USA. Electronic address: laurent.verkoczy@absinstitute.org.
Rogier W SandersDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA. Electronic address: r.w.sanders@amsterdamumc.nl.
Amsterdam University Medical Centers · NLDuke University · USScripps Research Institute · USCornell University · USApplied Biotechnology Institute · USUniversity of Southampton · GBSan Diego Biomedical Research Institute · US
Funding
Virus biology scientific research support componentUM1AI100645 · NIAID · DUKE UNIVERSITY · PI KELSOE, GARNETT H · 2012 to 2018
$204.7MIdentification 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
$190.4MStructural 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 · 2020 to 2026
$34.3MMPER broadly neutralizing antibody knockin mice to study anti-HIV Bcell responsesR01AI087202 · NIAID · SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE · PI VERKOCZY, LAURENT KARL · 2010 to 2022
$5.5MNeutralization of Primate Immunodeficiency VirusesR01AI036082 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI JOHN P MOORE · 1994 to 2026
$4.3MNIAID NIH HHS HHSN272201800004CNIAID NIH HHS P01 AI110657NIAID NIH HHS R01 AI036082NIAID NIH HHS R01 AI087202NIAID NIH HHS UM1 AI100645NIAID NIH HHS UM1 AI144371NIAID NIH HHS UM1 AI144462NIGMS NIH HHS P30 GM138396
Abstract
Targeting germline (gl-) precursors of broadly neutralizing antibodies (bNAbs) is acknowledged as an important strategy for HIV-1 vaccines. The VRC01-class of bNAbs is attractive because of its distinct genetic signature. However, VRC01-class bNAbs often require extensive somatic hypermutation, including rare insertions and deletions. We describe a BG505 SOSIP trimer, termed GT1.2, to optimize binding to gl-CH31, the unmutated common precursor of the CH30-34 bNAb lineage that acquired a large CDRH1 insertion. The GT1.2 trimer activates gl-CH31 naive B cells in knock-in mice, and B cell responses could be matured by selected boosting immunogens to generate cross-reactive Ab responses. Next-generation B cell sequencing reveals selection for VRC01-class mutations, including insertions in CDRH1 and FWR3 at positions identical to VRC01-class bNAbs, as well as CDRL1 deletions and/or glycine substitutions to accommodate the N276 glycan. These results provide proof of concept for vaccine-induced affinity maturation of B cell lineages that require rare insertions and deletions.
Indexed as
HIV-1HIV SeropositivityAnimalsAntibodies, NeutralizingBroadly Neutralizing AntibodiesHIV AntibodiesMiceVaccinationAntibodies, NeutralizingBroadly Neutralizing AntibodiesHIV AntibodiesbNAbsdeletionsgermline-targetingHIV-1 Envinsertionsmouse modelneutralizing antibodiesNGSvaccines
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