ArticleProceedings of the National Academy of Sciences of the United States of America2016
Epitope specificity plays a critical role in regulating antibody-dependent cell-mediated cytotoxicity against influenza A virus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.
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Who cites it
142 citing papers in PubMed, 187 citations in OpenAlex.
- Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens.Vaccine · 2025Trial
- Induction of Cross-Clade Antibody and T-Cell Responses by a Modified Vaccinia Virus Ankara-Based Influenza A(H5N1) Vaccine in a Randomized Phase 1/2a Clinical Trial.The Journal of infectious diseases · 2018Trial
- Influenza.Nature reviews. Disease primers · 2026Review
- Counteracting Influenza Virus Evolution Through the Full Spectrum of Broadly Protective Antibodies.Immunological reviews · 2026Review
- Determinants of natural killer cell-mediated antibody dependent cellular cytotoxicity in SARS-CoV-2 antibodies.PLoS pathogens · 2026Article
- Developments in genital herpes: progress in prevention and treatment.Current opinion in infectious diseases · 2026Review
- Purification and immunogenicity of Nipah virus-like particles from insect cells.BMC biotechnology · 2025Article
- The Yin and Yang of Antibodies in Viral Infectious Diseases.Diseases (Basel, Switzerland) · 2025Review
- Induction of hemagglutinin stalk reactive antibodies by the administration of a live-attenuated influenza virus vaccine in children.iScience · 2025Article
- Divergent antibody recognition profiles are generated by protective mRNA vaccines against Marburg and Ravn viruses.Nature communications · 2025Article
- Molecular parameters governing antibody FcγR signaling and effector functions in the context of HIV envelope.Cell reports · 2025Article
- Intranasal administration of a panreactive influenza antibody reveals Fc-independent mode of protection.Scientific reports · 2025Article
- Low-inflammatory lipid nanoparticle-based mRNA vaccine elicits protective immunity against H5N1 influenza virus with reduced adverse reactions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- How Broadly Neutralising Antibodies Are Redefining Immunity to Influenza.Antibodies (Basel, Switzerland) · 2025Review
- Influenza-specific antibody-mediated and complement-dependent cellular cytotoxicity-inducing antibodies in vaccinated and infected pigs.Frontiers in immunology · 2025Article
- Immune imprinting: The persisting influence of the first antigenic encounter with rapidly evolving viruses.Human vaccines & immunotherapeutics · 2024Review
- One HA stalk topping multiple heads as a novel influenza vaccine.Emerging microbes & infections · 2024Article
- Preclinical evaluation of a universal inactivated influenza B vaccine based on the mosaic hemagglutinin-approach.NPJ vaccines · 2024Article
- Fc-FcγR interactions during infections: From neutralizing antibodies to antibody-dependent enhancement.Immunological reviews · 2024Review
- Selection, Design and Immunogenicity Studies of ASFV Antigens for Subunit mRNA Cocktail Vaccines with Specific Immune Response Profiles.bioRxiv : the preprint server for biology · 2024Article
82 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The generation of strain-specific neutralizing antibodies against influenza A virus is known to confer potent protection against homologous infections. The majority of these antibodies bind to the hemagglutinin (HA) head domain and function by blocking the receptor binding site, preventing infection of host cells. Recently, elicitation of broadly neutralizing antibodies which target the conserved HA stalk domain has become a promising "universal" influenza virus vaccine strategy. The ability of these antibodies to elicit Fc-dependent effector functions has emerged as an important mechanism through which protection is achieved in vivo. However, the way in which Fc-dependent effector functions are regulated by polyclonal influenza virus-binding antibody mixtures in vivo has never been defined. Here, we demonstrate that interactions among viral glycoprotein-binding antibodies of varying specificities regulate the magnitude of antibody-dependent cell-mediated cytotoxicity induction. We show that the mechanism responsible for this phenotype relies upon competition for binding to HA on the surface of infected cells and virus particles. Nonneutralizing antibodies were poor inducers and did not inhibit antibody-dependent cell-mediated cytotoxicity. Interestingly, anti-neuraminidase antibodies weakly induced antibody-dependent cell-mediated cytotoxicity and enhanced induction in the presence of HA stalk-binding antibodies in an additive manner. Our data demonstrate that antibody specificity plays an important role in the regulation of ADCC, and that cross-talk among antibodies of varying specificities determines the magnitude of Fc receptor-mediated effector functions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.