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Licensed H5N1 vaccines generate cross-neutralizing antibodies against highly pathogenic H5N1 clade 2.3.4.4b influenza virus
Abstract
The emergence of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b viruses and their transmission to dairy cattle and animals, including humans, poses a major global public health threat. Therefore, the development of effective vaccines and therapeutics against H5N1 clade 2.3.4.4b virus is considered a public health priority. In the United States, three H5N1 vaccines derived from earlier strains of HPAI H5N1 (A/Vietnam, clade 1, and A/Indonesia, clade 2.1) virus, with (MF59 or AS03) or without adjuvants, are licensed and stockpiled for pre-pandemic preparedness, but whether they can elicit neutralizing antibodies against circulating H5N1 clade 2.3.4.4b viruses is unknown. In this study, we evaluated the binding, hemagglutination inhibition and neutralizing antibody response generated after vaccination of adults with the three licensed vaccines. Individuals vaccinated with the two adjuvanted licensed H5N1 vaccines generated cross-reactive binding and cross-neutralizing antibodies against the HPAI clade 2.3.4.4b A/Astrakhan/3212/2020 virus. Seroconversion rates of 60-95% against H5 clade 2.3.4.4b were observed after two doses of AS03-adjuvanted-A/Indonesia or three doses of MF59-adjuvanted-A/Vietnam vaccine. These findings suggest that the stockpiled US-licensed adjuvanted H5N1 vaccines generate cross-neutralizing antibodies against circulating HPAI H5N1 clade 2.3.4.4b in humans and may be useful as bridging vaccines until updated H5N1 vaccines become available.
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A stockpiled H5N1 vaccine utilizing the clade 1 A/Vietnam HA can elicit cross-neutralizing antibodies to clade 2.3.4.4b H5N1 in vaccinated humans, though the report did not evaluate contemporary 2024 H5N1 isolates.
“It has recently been reported that a stockpiled H5N1 vaccine utilizing the clade 1A/Vietnam HA can elicit cross-neutralizing antibodies to clade 2.3.4.4b H5N1 in vaccinated humans29, though the report did not evaluate contemporary 2024 H5N1 isolates.”
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 [29]
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Metadata
- Authors
- Khurana, S., King, L. R., Manischewitz, J., Posadas, O., Mishra, A. K., Liu, D., Beigel, J. H., Rappuoli, R., Tsang, J. S., & Golding, H.
- Affiliations
- Center for Biologics Evaluation and Research (US)
- National Institutes of Health (US)
- Corresponding author
- Khurana, Surender
- ORCID
- Venue
- Nature Medicine
- Published
- 2024-07-16
- Volume
- 30
- Issue
- 10
- Pages
- 2771-2776
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W4400691394
- Cited by
- 57
- References
- 21
- Citations by year
- 2026: 18 · 2025: 32 · 2024: 7
- FWCI
- 17.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Health and Human Services (MCMi OCET 2023-0229)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Outbreaks Research
- Keywords
- H5N1 influenza vaccine, clade 2.3.4.4b, cross-neutralizing antibodies, cross-reactive antibodies, adjuvanted vaccine, MF59, AS03, seroconversion, hemagglutination inhibition, binding antibodies, avian influenza
- MeSH terms
- Adjuvants, Immunologic, Adult, Animals, Antibodies, Viral, Cross Reactions, Female, Hemagglutination Inhibition Tests, Humans, Influenza, Human, Influenza Vaccines, Male, Middle Aged, Vaccination, Influenza A Virus, H5N1 Subtype, Young Adult, Antibodies, Neutralizing
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