ArticleImmunity2024
Eliciting a single amino acid change by vaccination generates antibody protection against group 1 and group 2 influenza A viruses.
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Article in Immunity, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24citing papers in PubMed
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Who cites it
24 citing papers in PubMed, 21 citations in OpenAlex.
- Epistasis and pleiotropy constrain the evolution of cross-reactive breadth in a broadly neutralizing influenza antibody.PLoS biology · 2026Article
- What Antibody Repertoires See: Structural and Immunogenetic Insights Into Influenza A Virus Hemagglutinin Recognition.Immunological reviews · 2026Review
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- CRISPR-mediated precise large fragment insertion in zygotes enables rapid generation of humanized immunoglobulin heavy-chain mice.Immunity · 2026Article
- Counteracting Influenza Virus Evolution Through the Full Spectrum of Broadly Protective Antibodies.Immunological reviews · 2026Review
- The Influenza-Specific Immunoglobulin Repertoire - Nimble Yet Steeped in Tradition.Immunological reviews · 2026Review
- Germinal center-independent memory B cells provide rapid protection from lethal influenza challenges.bioRxiv : the preprint server for biology · 2026Article
- Article
- Article
- Naturally self-reactive B cells are poised to cross the selection barrier into autoimmune germinal centers.Cell reports · 2026Article
- Highly Conserved Influenza A Nucleoprotein as a Target for Broad-Spectrum Intervention: Characterization of a Monoclonal Antibody with Pan-Influenza Reactivity.Veterinary sciences · 2026Article
- Broad-spectrum inhibition of influenza A virus replication by blocking the nuclear export of viral ribonucleoprotein complexes.Journal of virology · 2025Article
- A single mutation at position 214 of influenza B hemagglutinin enhances cross-neutralization.Emerging microbes & infections · 2025Article
- Functional Activity of HIV-1 bNAbs Across Diverse Strains is Driven by Binding Site and Can be Enhanced Through Fc Engineering.bioRxiv : the preprint server for biology · 2025Article
- Article
- Vulnerability in the breadth evolution of an influenza broadly neutralizing antibody.bioRxiv : the preprint server for biology · 2025Article
- Simultaneous priming of HIV broadly neutralizing antibody precursors to multiple epitopes by germline-targeting mRNA-LNP immunogens in mouse models.Science immunology · 2025Article
- Innate immunity and training to subvert original antigenic sin by the humoral immune response.eLife · 2025Article
- Functional and epitope specific monoclonal antibody discovery directly from immune sera using cryo-EM.Science advances · 2025Article
- Distinct binding modes drive the broad neutralization profile of two persistent influenza hemagglutinin stem-specific antibody lineages.Structure (London, England : 1993) · 2025Article
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Authors and funding
25 authors at 5 institutions in 2 countries.
Rashmi RayThe Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
Faez Amokrane Nait MohamedThe Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA. Electronic address: fnaitmohamed@mgh.harvard.edu.
Daniel P MaurerThe Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
Jiachen HuangDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Berk A AlpaySystems, Synthetic, and Quantitative Biology Program, Harvard University, Cambridge, MA 02138, USA; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
Larance RonsardThe Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
Zhenfei XieThe Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
Julianna HanDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Monica Fernandez-QuinteroDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of General, Inorganic and Theoretical Chemistry, Center for Chemistry and Biomedicine, University of Innsbruck, Innrain 80-82/III, 6020 Innsbruck, Austria.
Quynh Anh PhanThe Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
Rebecca L UrsinThe Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
Mya VuThe Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
Kathrin H KirschThe Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
Thavaleak PrumThe Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
Victoria C RosadoThe Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
Thalia Bracamonte-MorenoThe Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
Vintus OkonkwoThe Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
Julia BalsThe Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
Caitlin McCarthyThe Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
Usha NairThe Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
Masaru KanekiyoVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892-3005, USA.
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Aaron G SchmidtThe Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: aschmidt@crystal.harvard.edu.
Facundo D BatistaThe Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA; Department of Biology, The Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: fbatista1@mgh.harvard.edu.
Daniel LingwoodThe Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA. Electronic address: dlingwood@mgh.harvard.edu.
Ragon Institute of MGH, MIT and Harvard · USScripps Research Institute · USHarvard University · USNational Institutes of Health · USUniversität Innsbruck · AT
Funding
The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ARTHUR Y KIM · 2004 to 2026
$94.4MInfluenza Vaccine Research and DevelopmentZIAAI005003 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI KANEKIYO, MASARU · 2009 to 2025
$89.8MUsing a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5MVirology CoreP01AI089618 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI STEPHEN COPLAN HARRISON · 2011 to 2026
$40.0MEpitope focusing to the receptor binding motif for a universal coronavirus vaccineR01AI146779 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI SCHMIDT, AARON GREGORY · 2019 to 2023
$4.2MInnate-like BCR activity as a template for universal vaccination against influenza virusR01AI137057 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI CHACKERIAN, BRYCE C, LINGWOOD, DANIEL · 2018 to 2022
$2.6MTriggering germline-encoded broadly neutralizing antibody responses against influenza virusR01AI153098 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI BATISTA, FACUNDO DAMIAN, LINGWOOD, DANIEL · 2020 to 2023
$2.1MCDRH3-independent B cell stimulation to selectively expand VRC01 lineages from a fully humanized immunoglobulin repertoireR01AI124378 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI CHACKERIAN, BRYCE C, LINGWOOD, DANIEL · 2017 to 2020
$2.0MSystemic coordination of pro-inflammatory immune reactions through dendritic cell-restricted sIL6R biogenesisR01AI155447 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI LINGWOOD, DANIEL · 2021 to 2025
$2.0MGates Foundation INV-004923NIAID NIH HHS P01 AI089618NIAID NIH HHS P30 AI060354NIAID NIH HHS R01 AI124378NIAID NIH HHS R01 AI137057NIAID NIH HHS R01 AI146779NIAID NIH HHS R01 AI153098NIAID NIH HHS R01 AI155447NIAID NIH HHS U19 AI057229
Abstract
Broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem of influenza A viruses (IAVs) tend to be effective against either group 1 or group 2 viral diversity. In rarer cases, intergroup protective bnAbs can be generated by human antibody paratopes that accommodate the conserved glycan differences between the group 1 and group 2 stems. We applied germline-engaging nanoparticle immunogens to elicit a class of cross-group bnAbs from physiological precursor frequency within a humanized mouse model. Cross-group protection depended on the presence of the human bnAb precursors within the B cell repertoire, and the vaccine-expanded antibodies enriched for an N55T substitution in the CDRH2 loop, a hallmark of the bnAb class. Structurally, this single mutation introduced a flexible fulcrum to accommodate glycosylation differences and could alone enable cross-group protection. Thus, broad IAV immunity can be expanded from the germline repertoire via minimal antigenic input and an exceptionally simple antibody development pathway.
Indexed as
Antibodies, NeutralizingAntibodies, ViralInfluenza A virusInfluenza VaccinesOrthomyxoviridae InfectionsVaccinationAmino Acid SubstitutionAnimalsB-LymphocytesBroadly Neutralizing AntibodiesHemagglutinin Glycoproteins, Influenza VirusHumansInfluenza, HumanMiceAntibodies, NeutralizingAntibodies, ViralBroadly Neutralizing AntibodiesHemagglutinin Glycoproteins, Influenza VirusInfluenza Vaccineshuman antibody repertoireimmunogeninfluenza virussomatic hypermutationuniversalvaccine
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