Safety and Immunogenicity of Influenza A H5 Subunit Vaccines: Effect of Vaccine Schedule and Antigenic Variant
Open accessAbstract
BACKGROUND: The current US national stockpile of influenza H5 vaccine was produced using the antigen from the strain A/Vietnam/1203/2004 (a clade 1 H5 virus). Recent H5 disease has been caused by antigenically divergent H5 viruses, including A/Indonesia/05/2005 (a clade 2 H5 virus). METHODS: The influence of schedule on the antibody response to 2 doses of H5 vaccines (one a clade 1 hemagglutinin protein [HA] vaccine and one a clade 2 HA vaccine) containing 90 μg of antigen was evaluated in healthy adults 18-49 years of age. RESULTS: Two doses of vaccine were required to induce antibody titers ≥ 1:10 in most subjects. Accelerated schedules were immunogenic, and antibody developed after vaccinations on days 0 and 7, 0 and 14, and 0 and 28, with the day 0 and 7 schedule inducing lower titers than those induced with the other schedules. With mixed vaccine schedules of clade 1 followed by clade 2 vaccine administration, the first vaccination primed for a heterologous boost. The heterologous response was improved when the second vaccination was given 6 months after the first, compared with the response when the second vaccination was given after an interval of 1 month. CONCLUSIONS: An accelerated vaccine schedule of injections administered at days 0 and 14 was as immunogenic as a vaccine schedule of injections at days 0 and 28, but both schedules were inferior to a vaccine schedule of injections administered at 0 and 6 months for priming for heterologous vaccine boosting. Clinical Trial Registry Number: NCT00703053.
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Humans receiving two doses of an investigational H5 vaccine based on clade 2.1.3 A/Indonesia/05/2005 PR8-IBCDC-RG2 failed to elicit neutralizing antibodies against A/Vietnam or vice versa, and heterologous prime-boost was necessary to elicit cross-neutralizing antibody responses.
“Humans receiving two doses of an investigational H5 vaccine based on clade 2.1.3A/Indonesia/05/2005 PR8-IBCDC-RG2 failed to elicit neutralizing antibodies against A/Vietnam or vice versa and instead heterologous prime-boost was necessary to elicit cross-neutralizing antibody responses21.”
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 [21]
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- Authors
- Belshe, R. B., Frey, S. E., Graham, I., Mulligan, M. J., Edupuganti, S., Jackson, L. A., Wald, A., Poland, G., Jacobson, R., Keyserling, H. L., Spearman, P., Hill, H., Wolff, M., & for the National Institute of Allergy and Infectious Diseases–Funded Vaccine and Treatment Evaluation Units
- Affiliations
- Saint Louis University (US)
- Emory University (US)
- Kaiser Permanente Washington Health Research Institute (US)
- University of Washington (US)
- Mayo Clinic (US)
- Emmes (United States) (US)
- ORCID
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-03-01
- Volume
- 203
- Issue
- 5
- Pages
- 666-673
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- PMC
- PMC3071280
- OpenAlex
- W2013230062
- Cited by
- 62
- References
- 12
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 2 · 2017: 8 · 2016: 3 · 2015: 7 · 2014: 11 · 2013: 1 · 2012: 1
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1TR000454)
- U.S. Public Health Service (HHSN-272200800003C)
- National Institute of Allergy and Infectious Diseases (HHSN272200800004C, HHSN272200800005C)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- subunit vaccine, vaccination schedule, accelerated vaccination schedule, antigenic variants, heterologous booster, antibody response, hemagglutinin, vaccine immunogenicity, vaccine safety, pandemic influenza preparedness
- MeSH terms
- Adolescent, Adult, Antibodies, Viral, Antigenic Variation, Drug Administration Schedule, Female, Humans, Immunization, Secondary, Influenza, Human, Influenza Vaccines, Male, Middle Aged, Influenza A virus, Vaccines, Subunit, Influenza A Virus, H5N1 Subtype, Young Adult
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