ArticleImmunity2022
Membrane-bound mRNA immunogens lower the threshold to activate HIV Env V2 apex-directed broadly neutralizing B cell precursors in humanized mice.
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Article in Immunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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54citing papers in PubMed
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54 citing papers in PubMed, 61 citations in OpenAlex.
- Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans.Science (New York, N.Y.) · 2025Trial
- Targeting of conserved spike epitopes enables broad antibody neutralisation of diverse bat sarbecoviruses.PLoS biology · 2026Article
- CRISPR-mediated precise large fragment insertion in zygotes enables rapid generation of humanized immunoglobulin heavy-chain mice.Immunity · 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
- Local antibody feedback enforces a checkpoint on affinity maturation in the germinal center and promotes epitope spreading.Immunity · 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
- Virus glycoprotein nanodisc platform for vaccine analytics.Nature communications · 2026Article
- Accelerating Innovation: Advancing Opportunities in HIV Vaccine Development.Current HIV research · 2026Review
- Germline-Targeting Strategies to Induce bNAbs against HIV-1.Current HIV research · 2026Review
- Innovative Single-Cell Sequencing Techniques for B cell Analysis and Their Implications for Rational HIV-1 Vaccine Design.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
- Antibody feedback establishes an affinity brake in the germinal center.bioRxiv : the preprint server for biology · 2025Article
- Review
- Germline-targeting HIV immunogen induces cross-neutralizing antibodies in outbred macaques.bioRxiv : the preprint server for biology · 2025Article
- Simultaneous induction of multiple classes of broadly neutralizing antibody precursors by combination germline-targeting immunization in nonhuman primates.Science immunology · 2025Article
- Simultaneous priming of HIV broadly neutralizing antibody precursors to multiple epitopes by germline-targeting mRNA-LNP immunogens in mouse models.Science immunology · 2025Article
- Structural and genetic basis of HIV-1 envelope V2 apex recognition by rhesus broadly neutralizing antibodies.The Journal of experimental medicine · 2025Article
- Augmented humoral responses to HIV Env trimers delivered as transmembrane immunogens by self-replicating RNA.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
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Authors and funding
24 authors at 4 institutions in 1 country.
Eleonora MelziThe Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Jordan R WillisDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Krystal M MaDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Ying-Cing LinThe Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Sven KratochvilThe Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Zachary T BerndsenDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Elise A LandaisDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Oleksandr KalyuzhniyDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Usha NairThe Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
John WarnerThe Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Jon M SteichenDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Anton KalyuzhniyDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Amber LeDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Simone PecettaThe Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Manfredo PerezThe Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Kathrin KirschThe Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Stephanie R WeldonThe Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Samantha FalconeModerna Inc., Cambridge, MA 02139, USA.
Sunny HimansuModerna Inc., Cambridge, MA 02139, USA.
Andrea CarfiModerna Inc., Cambridge, MA 02139, USA.
Devin SokDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Andrew B WardInternational AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium 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.
William R SchiefThe Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: schief@scripps.edu.
Facundo D BatistaThe Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Immunology, Harvard Medical School, Boston, MA, USA; Department of Microbiology, Harvard Medical School, Boston, MA, USA. Electronic address: fbatista1@mgh.harvard.edu.
Scripps Research Institute · USRagon Institute of MGH, MIT and Harvard · USModerna Therapeutics (United States) · USHarvard University · US
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
$201.6MSupport Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI MCELRATH, MARGARET JULIANA · 2012 to 2018
$131.5MUC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3MVirologyP30AI036214 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI David Mitchell Smith · 1994 to 2026
$78.4MNCATS NIH HHS UL1 TR001442NIAID NIH HHS P30 AI036214NIAID NIH HHS UM1 AI100663NIAID NIH HHS UM1 AI144462
Abstract
Eliciting broadly neutralizing antibodies (bnAbs) is the core of HIV vaccine design. bnAbs specific to the V2-apex region of the HIV envelope acquire breadth and potency with modest somatic hypermutation, making them attractive vaccination targets. To evaluate Apex germline-targeting (ApexGT) vaccine candidates, we engineered knockin (KI) mouse models expressing the germline B cell receptor (BCR) of the bnAb PCT64. We found that high affinity of the ApexGT immunogen for PCT64-germline BCRs was necessary to specifically activate KI B cells at human physiological frequencies, recruit them to germinal centers, and select for mature bnAb mutations. Relative to protein, mRNA-encoded membrane-bound ApexGT immunization significantly increased activation and recruitment of PCT64 precursors to germinal centers and lowered their affinity threshold. We have thus developed additional models for HIV vaccine research, validated ApexGT immunogens for priming V2-apex bnAb precursors, and identified mRNA-LNP as a suitable approach to substantially improve the B cell response.
Indexed as
AIDS VaccinesHIV-1HIV InfectionsAnimalsAntibodies, NeutralizingBroadly Neutralizing Antibodiesenv Gene Products, Human Immunodeficiency VirusHIV AntibodiesHumansMiceRNA, MessengerAIDS VaccinesAntibodies, NeutralizingBroadly Neutralizing Antibodiesenv Gene Products, Human Immunodeficiency VirusHIV AntibodiesRNA, MessengerantibodyB cell receptorbnAbsHIV vaccineimmunizationknockinmRNAV2 apex
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