ArticleNature medicine2014
Broadly neutralizing hemagglutinin stalk-specific antibodies require FcγR interactions for protection against influenza virus in vivo.
Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 556 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
556 citing papers in PubMed, 759 citations in OpenAlex.
- Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens.Vaccine · 2025Trial
- Hemagglutinin Stalk-Specific Fc-Mediated Functions Are Associated With Protection Against Influenza Illness After Seasonal Influenza Vaccination.The Journal of infectious diseases · 2024Trial
- Dissecting Fc signatures of protection in neonates following maternal influenza vaccination in a placebo-controlled trial.Cell reports · 2022Trial
- Safety and immunogenicity of a ferritin nanoparticle H2 influenza vaccine in healthy adults: a phase 1 trial.Nature medicine · 2022Trial
- A systems approach to elucidate personalized mechanistic complexities of antibody-Fc receptor activation post-vaccination.Cell reports. Medicine · 2021Trial
- A bispecific antibody targeting conserved hemagglutinin epitopes confers broad protection against H7 avian influenza and accelerates viral clearance via localized respiratory delivery.Emerging microbes & infections · 2026Article
- Polyclonal breast milk-derived secretory IgA confers broad antiviral protection against multiple respiratory viruses.Science advances · 2026Article
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- An In Vitro Screen Identifies H1 Influenza Hemagglutinin Substitutions That Alter mRNA-LNP Vaccine Responses Against the Stalk Domain.Vaccines · 2026Article
- Tuberculosis treatment and cytotoxic immune signatures: a longitudinal study.Journal of clinical tuberculosis and other mycobacterial diseases · 2026Article
- Counteracting Influenza Virus Evolution Through the Full Spectrum of Broadly Protective Antibodies.Immunological reviews · 2026Review
- Optimizing an avian influenza vaccine using a novel Bacterial Enzymatic Combinatorial Chemistry (BECC) TLR4 adjuvant.mSphere · 2026Article
- Elicitation of stem-directed antibodies in rhesus macaques by a conventional hemagglutinin immunogen.bioRxiv : the preprint server for biology · 2026Article
- Germinal center-independent memory B cells provide rapid protection from lethal influenza challenges.bioRxiv : the preprint server for biology · 2026Article
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- Prior immunity to seasonal influenza A(H3N2) virus confers varying levels of cross-protection against challenge with clade 2.3.4.4b A(H5N1), A(H7N9), or A(H9N2) virus in a ferret model.Microbiology spectrum · 2026Article
- A dual-adjuvanted HA stem nanoparticle vaccine elicits a multifunctional antibody response that is associated with protection in newborn monkeys.Cell reports. Medicine · 2026Article
- Fc-engineered antibodies enhance protection against SARS-CoV-2 lung infection and inflammation.mBio · 2026Article
- Preexisting IgG forms immune complexes and links local thermal reactogenicity with immunogenicity in influenza vaccination.NPJ vaccines · 2026Article
496 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Neutralizing antibodies against influenza viruses have traditionally been thought to provide protection exclusively through their variable region; the contributions of mechanisms conferred by the Fc domain remain controversial. We investigated the in vivo contributions of Fc interactions with their cognate receptors for a collection of neutralizing anti-influenza antibodies. Whereas five broadly neutralizing monoclonal antibodies (bNAbs) targeting the conserved stalk region of hemagglutinin (HA) required interactions between the antibody Fc and Fc receptors for IgG (FcγRs) to confer protection from lethal H1N1 challenge, three strain-specific monoclonal Abs (mAbs) against the variable head domain of HA were equally protective in the presence or absence of FcγR interactions. Although all antibodies blocked infection, only anti-stalk bNAbs were capable of mediating cytotoxicity of infected cells, which accounts for their FcγR dependence. Immune complexes generated with anti-HA stalk mAb efficiently interacted with FcγRs, but anti-HA head immune complexes did not. These results suggest that FcγR binding capacity by anti-HA antibodies was dependent on the interaction of the cognate Fab with antigen. We exploited these disparate mechanisms of mAb-mediated protection to reengineer an anti-stalk bNAb to selectively enhance FcγR engagement to augment its protective activity. These findings reveal a previously uncharacterized property of bNAbs and guide an approach toward enhancing mAb-mediated antiviral therapeutics.
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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.