Induction of broadly cross-reactive antibody responses to the influenza HA stem region following H5N1 vaccination in humans
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Significance: Vaccination is the most effective means of attaining protection against influenza viruses. However, the constantly evolving nature of influenza viruses enables them to escape preexisting immune surveillance, and thus thwarts public health efforts to control influenza annual epidemics and occasional pandemics. One solution is to elicit antibodies directed against highly conserved epitopes, such as those within the stem region of influenza HA, the principal target of virus-neutralizing antibody responses. This study shows that annual influenza vaccines induce antibody responses that are largely directed against the highly variable HA head region. In contrast, heterologous immunization with HA derived from influenza strains that are currently not circulating in humans (e.g. H5N1) can substantially increase HA stem-specific responses.
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Pre-existing immunity to influenza may improve the breadth of responses elicited by H5 HA vaccines.
“These data support the hypothesis that pre-existing immunity to influenza may improve the breadth of responses elicited by H5 HA vaccines.”
From Clade 2.3.4.4b but not historical clade 1 HA replicating RNA vaccine protects against bovine H5N1 challenge in mice (2025) · cites this paper as [11]
The HA head domain is an immunodominant target of vaccine-induced immunity.
“the HA head is an immunodominant target of vaccine-induced immunity11”
From Clade 2.3.4.4b but not historical clade 1 HA replicating RNA vaccine protects against bovine H5N1 challenge in mice (2025) · cites this paper as [11]
Humans with pre-existing influenza immunity vaccinated with an H5 vaccine developed greater broadly neutralizing antibody responses.
“Humans with pre-existing influenza immunity vaccinated with an H5 vaccine developed greater broadly neutralizing antibody responses11, suggesting pre-existing immunity may improve the breadth of response to H5N1 vaccination.”
From Clade 2.3.4.4b but not historical clade 1 HA replicating RNA vaccine protects against bovine H5N1 challenge in mice (2025) · cites this paper as [11]
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- Authors
- Ellebedy, A. H., Krammer, F., Li, G.-M., Miller, M. S., Chiu, C., Wrammert, J., Chang, C. Y., Davis, C. W., McCausland, M., Elbein, R., Edupuganti, S., Spearman, P., Andrews, S. F., Wilson, P. C., García-Sastre, A., Mulligan, M. J., Mehta, A. K., Palese, P., & Ahmed, R.
- Affiliations
- Emory University (US)
- Department of Microbiology,
- Department of Microbiology and Immunology,
- Division of Infectious Diseases, Department of Medicine,
- Department of Pediatrics,
- University of Chicago (US)
- HOPE Clinic (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-08-25
- Volume
- 111
- Issue
- 36
- Pages
- 13133-13138
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4246941
- OpenAlex
- W1993577147
- Cited by
- 234
- References
- 42
- Citations by year
- 2026: 13 · 2025: 24 · 2024: 12 · 2023: 8 · 2022: 13 · 2021: 24 · 2020: 24 · 2019: 24 · 2018: 30 · 2017: 21 · 2016: 21 · 2015: 19 · 2014: 1
- FWCI
- 15.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Georgia Research Alliance
- Children's Healthcare of Atlanta
- National Institute for Health and Care Research (NF-SI-0513-10150)
- Austrian Science Fund (J 3232)
- National Institutes of Health (HHSN272200800005C, UL1TR000454, P51OD011132)
- U.S. Public Health Service (HHSN26620070010C)
- Canadian Institutes of Health Research
- Medical Research Council (MC_G1001212)
- National Institute of Allergy and Infectious Diseases (U19AI109946, P01AI097092, HHSN266200700006C, HHSN26620070010C, HHSN272200800005C, U19AI082724, T32AI074492)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- influenza virus, broadly neutralizing antibodies, seasonal influenza vaccination, memory B cells, cross-reactive antibody response, conserved epitopes, heterologous immunization, pandemic influenza preparedness, B cell response
- MeSH terms
- Adult, Antibody Formation, Antibody Specificity, Cross Reactions, Humans, Immunoglobulin G, Immunologic Memory, Influenza, Human, Influenza Vaccines, Plasma Cells, Vaccination, Hemagglutinin Glycoproteins, Influenza Virus, Influenza A Virus, H5N1 Subtype
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