ArticleProceedings of the National Academy of Sciences of the United States of America2020
Original antigenic sin priming of influenza virus hemagglutinin stalk antibodies.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 103 citations in OpenAlex.
- Effects of Age and Birth Cohort on Influenza A Virus Subtype-Specific Hospitalization Rates, United States, 2010-2025.The Journal of infectious diseases · 2026Article
- Article
- What Antibody Repertoires See: Structural and Immunogenetic Insights Into Influenza A Virus Hemagglutinin Recognition.Immunological reviews · 2026Review
- Computational Design and Expression of Headless Influenza Hemagglutinin Antigens Toward a Modular Universal Nanoparticle Vaccine.Antibodies (Basel, Switzerland) · 2026Article
- Persistence of memory: lifespan dynamics of the human antiviral antibody reactome.Nature communications · 2026Article
- SARS-CoV-2 Omicron infection reveals imprinted antibody responses in the absence of vaccination.iScience · 2026Article
- Influenza Vaccination Effectiveness Against Influenza-Associated Hospitalization in Children and the Effects of Repeated Vaccination.The Journal of infectious diseases · 2026Article
- Pre-existing influenza antibodies, younger age, and increased CD4 THuman immunology · 2026Article
- Article
- Immune Priming and the Risk of COVID-19, Influenza, and Other Acute Respiratory Infections: Insights From an N3C Cohort.Influenza and other respiratory viruses · 2026Article
- A 14-year influenza reinfection surveillance in Chongqing, China: A retrospective analysis.Human vaccines & immunotherapeutics · 2025Article
- H1N1 challenge results in rapid recall of stem-specific immunity in HA stem nanoparticle-vaccinated newborn monkeys.JCI insight · 2025Article
- Influenza vaccine based on AS03-adjuvanted chimeric HA induces long-lived stalk-specific plasma cells in bone marrow and lymph nodes of nonhuman primates.Nature immunology · 2025Article
- Innate immunity and training to subvert original antigenic sin by the humoral immune response.eLife · 2025Article
- H3 hemagglutinin proteins optimized for 2018 to 2022 elicit neutralizing antibodies across panels of modern influenza A(H3N2) viruses.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Immune history shapes human antibody responses to H5N1 influenza viruses.Nature medicine · 2025Article
- Antigenic drift expands influenza viral escape pathways from recalled humoral immunity.Immunity · 2025Article
- Differential antigenic imprinting effects between influenza H1N1 hemagglutinin and neuraminidase in a mouse model.Journal of virology · 2025Article
- Phenomenological Modeling of Antibody Response from Vaccine Strain Composition.Antibodies (Basel, Switzerland) · 2025Article
- A paradigm shift in simulating affinity maturation to elicit broadly neutralizing antibodies.Frontiers in immunology · 2025Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Immunity to influenza viruses can be long-lived, but reinfections with antigenically distinct viral strains and subtypes are common. Reinfections can boost antibody responses against viral strains first encountered in childhood through a process termed "original antigenic sin." It is unknown how initial childhood exposures affect the induction of antibodies against the hemagglutinin (HA) stalk domain of influenza viruses. This is an important consideration since broadly reactive HA stalk antibodies can protect against infection, and universal vaccine platforms are being developed to induce these antibodies. Here we show that experimentally infected ferrets and naturally infected humans establish strong "immunological imprints" against HA stalk antigens first encountered during primary influenza virus infections. We found that HA stalk antibodies are surprisingly boosted upon subsequent infections with antigenically distinct influenza A virus subtypes. Paradoxically, these heterosubtypic-boosted HA stalk antibodies do not bind efficiently to the boosting influenza virus strain. Our results demonstrate that an individual's HA stalk antibody response is dependent on the specific subtype of influenza virus that they first encounter early in life. We propose that humans are susceptible to heterosubtypic influenza virus infections later in life since these viruses boost HA stalk antibodies that do not bind efficiently to the boosting antigen.
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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.