ArticlePLoS pathogens2017
A structural explanation for the low effectiveness of the seasonal influenza H3N2 vaccine.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03734237 (A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD), which is not on this map. Cited by 147 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD
Who cites it
147 citing papers in PubMed, 2 syntheses or guidelines pooled it, 230 citations in OpenAlex.
- Relative Effectiveness of Cell-Cultured versus Egg-Based Seasonal Influenza Vaccines in Preventing Influenza-Related Outcomes in Subjects 18 Years Old or Older: A Systematic Review and Meta-Analysis.International journal of environmental research and public health · 2022Pooled it
- Moving the Needle on Atherosclerotic Cardiovascular Disease and Heart Failure with Influenza Vaccination.Current atherosclerosis reports · 2021Pooled it
- Immunogenicity and safety of 1 versus 2 doses of quadrivalent-inactivated influenza vaccine in children aged 3-8 years with or without previous influenza vaccination histories.Human vaccines & immunotherapeutics · 2025Trial
- Recombinant vs Egg-Based Quadrivalent Influenza Vaccination for Nursing Home Residents: A Cluster Randomized Trial.JAMA network open · 2025Trial
- Redirecting antibody responses from egg-adapted epitopes following repeat vaccination with recombinant or cell culture-based versus egg-based influenza vaccines.Nature communications · 2024Trial
- Induction of Cross-Reactive Hemagglutination Inhibiting Antibody and Polyfunctional CD4+ T-Cell Responses by a Recombinant Matrix-M-Adjuvanted Hemagglutinin Nanoparticle Influenza Vaccine.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Trial
- VirPLM: antigenic prediction of influenza A/H3N2 viruses with a fine-tuned protein language model.Bioinformatics (Oxford, England) · 2026Article
- Seasonal influenza mRNA vaccine induces stronger innate and comparable or better adaptive responses than licensed inactivated vaccines.NPJ vaccines · 2026Article
- A semi-replicating VSV (srVSV)-based platform for developing broad-spectrum mucosal vaccines against influenza A viruses.Virologica Sinica · 2026Article
- Low effectiveness of influenza vaccines vis-à-vis mechanism of protection by vaccines - potential causes and recommendations to improve control of influenza.Frontiers in immunology · 2026Review
- Porcine influenza mAbs to H3, H5, and H7 hemagglutinins recognize H3 egg adapted site and target the HA stem.Discovery immunology · 2026Article
- mRNA-based seasonal influenza vaccines: an overview of immunogenicity, efficacy, and safety.Frontiers in immunology · 2026Review
- Presentation of hemagglutinin on adjuvant-bearing self-assembling peptide nanofibers increases heterologous responses against influenza.Acta biomaterialia · 2026Article
- Structural and immunological characterization of the H3 influenza hemagglutinin during antigenic drift.Nature communications · 2025Article
- Australian preferences for influenza vaccine attributes and cost: A discrete choice experiment.Human vaccines & immunotherapeutics · 2025Article
- Estimated Relative Effectiveness and Public Health Impact of Cell-Based Versus Egg-Based Influenza Vaccines During the 2022-2023 Season in the United States.Influenza and other respiratory viruses · 2025Article
- Structure and function of a cross-neutralizing influenza neuraminidase antibody that accommodates recent N2 NA Asn245 glycosylation.Communications biology · 2025Article
- Effects of repeated influenza vaccination and infection on durable seroprotection in healthcare workers.NPJ vaccines · 2025Article
- Epistasis in the receptor-binding domain of contemporary H3N2 viruses that reverted to bind sialylated di-LacNAc repeats.Cell reports · 2025Article
- Article
87 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The effectiveness of the annual influenza vaccine has declined in recent years, especially for the H3N2 component, and is a concern for global public health. A major cause for this lack in effectiveness has been attributed to the egg-based vaccine production process. Substitutions on the hemagglutinin glycoprotein (HA) often arise during virus passaging that change its antigenicity and hence vaccine effectiveness. Here, we characterize the effect of a prevalent substitution, L194P, in egg-passaged H3N2 viruses. X-ray structural analysis reveals that this substitution surprisingly increases the mobility of the 190-helix and neighboring regions in antigenic site B, which forms one side of the receptor binding site (RBS) and is immunodominant in recent human H3N2 viruses. Importantly, the L194P substitution decreases binding and neutralization by an RBS-targeted broadly neutralizing antibody by three orders of magnitude and significantly changes the HA antigenicity as measured by binding of human serum antibodies. The receptor binding mode and specificity are also altered to adapt to avian receptors during egg passaging. Overall, these findings help explain the low effectiveness of the seasonal vaccine against H3N2 viruses, and suggest that alternative approaches should be accelerated for producing influenza vaccines as well as isolating clinical isolates.
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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.