Immunogenicity and Cross-Protective Efficacy Induced by an Inactivated Recombinant Avian Influenza A/H5N1 (Clade 2.3.4.4b) Vaccine against Co-Circulating Influenza A/H5Nx Viruses
Open accessAbstract
Controlling avian influenza viruses (AIVs) is mainly based on culling of the infected bird flocks or via the implementation of inactivated vaccines in countries where AIVs are considered to be endemic. Over the last decade, several avian influenza virus subtypes, including highly pathogenic avian influenza (HPAI) H5N1 clade 2.2.1.2, H5N8 clade 2.3.4.4b and the recent H5N1 clade 2.3.4.4b, have been reported among poultry populations in Egypt. This demanded the utilization of a nationwide routine vaccination program in the poultry sector. Antigenic differences between available avian influenza vaccines and the currently circulating H5Nx strains were reported, calling for an updated vaccine for homogenous strains. In this study, three H5Nx vaccines were generated by utilizing the reverse genetic system: rgH5N1_2.3.4.4, rgH5N8_2.3.4.4 and rgH5N1_2.2.1.2. Further, the immunogenicity and the cross-reactivity of the generated inactivated vaccines were assessed in the chicken model against a panel of homologous and heterologous H5Nx HPAIVs. Interestingly, the rgH5N1_2.3.4.4 induced high immunogenicity in specific-pathogen-free (SPF) chicken and could efficiently protect immunized chickens against challenge infection with HPAIV H5N1_2.3.4.4, H5N8_2.3.4.4 and H5N1_2.2.1.2. In parallel, the rgH5N1_2.2.1.2 could partially protect SPF chickens against infection with HPAIV H5N1_2.3.4.4 and H5N8_2.3.4.4. Conversely, the raised antibodies to rgH5N1_2.3.4.4 could provide full protection against HPAIV H5N1_2.3.4.4 and HPAIV H5N8_2.3.4.4, and partial protection (60%) against HPAIV H5N1_2.2.1.2. Compared to rgH5N8_2.3.4.4 and rgH5N1_2.2.1.2 vaccines, chickens vaccinated with rgH5N1_2.3.4.4 showed lower viral shedding following challenge infection with the predefined HPAIVs. These data emphasize the superior immunogenicity and cross-protective efficacy of the rgH5N1_2.3.4.4 in comparison to rgH5N8_2.3.4.4 and rgH5N1_2.2.1.2.
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Vaccination of chickens with recombinant viruses with clade 2.3.4.4 or 2.2.1.2 HAs showed strong homologous protection but incomplete heterologous protection.
“Vaccination of chickens with recombinant viruses with clade 2.3.4.4 or 2.2.1.2 HAs showed strong homologous protection but incomplete heterologous protection28 further suggesting that broad homosubtypic immunity may not always be achieved.”
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 [28]
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- Authors
- Mahmoud, S. H., Khalil, A. A., Abo Shama, N. M., El Sayed, M. F., Soliman, R. A., Hagag, N. M., Yehia, N., Naguib, M. M., Arafa, A.-S., Ali, M. A., El-Safty, M. M., & Mostafa, A.
- Affiliations
- National Research Centre (EG)
- Veterinary Serum and Vaccine Research Institute (EG)
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt
- Central Laboratory for Evaluation of Veterinary Biologics, Agricultural Research Center (ARC), Abbasia, Cairo 11517, Egypt
- Agricultural Research Center (EG)
- Uppsala University (SE)
- Reference Laboratory for Veterinary Quality Control on Poultry Production, Animal Health Research Institute, Agriculture Research Center, Giza 12618, Egypt
- Texas Biomedical Research Institute (US)
- Corresponding author
- Mostafa, Ahmed
- ORCID
- Venue
- Vaccines
- Publisher
- MDPI AG
- Published
- 2023-08-22
- Volume
- 11
- Issue
- 9
- Pages
- 1397
- ISSN
- 2076-393X (ISSN-L)
- PMC
- PMC10538193
- OpenAlex
- W4386072956
- Cited by
- 14
- References
- 43
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 4
- FWCI
- 2.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Vaccines (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Uppsala University Publications (Uppsala University) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Strategy for Genetic Engineering and Biotechnology, Academy of Scientific Research and Technology (ASRT), Egypt (TT110801, 12010126, CTS 21:1618, M2250, M22-0074, 2021-00833)
- Egyptian National Research Centre (NRC) (TT110801, 12010126, CTS 21:1618, M2250, M22-0074, 2021-00833)
- Carl Trygger Stiftelse (TT110801, 12010126, CTS 21:1618, M2250, M22-0074, 2021-00833)
- Clas Groschinskys Minnesfond (TT110801, 12010126, CTS 21:1618, M2250, M22-0074, 2021-00833)
- Åke Wibergs Stiftelse (TT110801, 12010126, CTS 21:1618, M2250, M22-0074, 2021-00833)
- Swedish Research Council for Sustainable Development-FORMAS (TT110801, 12010126, CTS 21:1618, M2250, M22-0074, 2021-00833)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- H5N1 avian influenza, H5N8, inactivated vaccine, recombinant vaccine, reverse genetics, cross-protective immunity, immunogenicity, heterologous challenge, clade 2.3.4.4b, poultry vaccination, antibody response, SPF chickens
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