» Articles » PMID: 39881325

Avian Influenza MRNA Vaccine Encoding Hemagglutinin Provides Complete Protection Against Divergent H5N1 Viruses in Specific-pathogen-free Chickens

Overview
Publisher Biomed Central
Date 2025 Jan 29
PMID 39881325
Authors
Affiliations
Soon will be listed here.
Abstract

Background: The rapid mutation of avian influenza virus (AIV) poses a significant threat to both the poultry industry and public health. Herein, we have successfully developed an mRNA-LNPs candidate vaccine for H5 subtype highly pathogenic avian influenza and evaluated its immunogenicity and protective efficacy.

Results: In experiments on BALB/c mice, the vaccine candidate elicited strong humoral and a certain cellular immune responses and protected mice from the heterologous AIV challenge. Antibody and splenocyte passive transfer assays in mice suggested that antibodies played a crucial role in providing protection. Experiments involving SPF chickens have revealed that two doses of the 5 µg vaccine candidate in this study provided 100% complete protection against homologous strains, but only 50% complete protection against heterologous strains. Even immunization with two doses of the 15 µg vaccine candidate resulted in 90% complete protection against heterologous strains. To enhance the immune efficacy of the candidate vaccine, we designed 6 sequences with different secondary structures and screened out the candidate sequence with the highest expression (SY2-HA mRNA). Experiments on SPF chickens showed that two doses of 5 µg SY2-HA mRNA-LNP vaccine provided 100% complete protection against homologous and heterologous H5N1 AIV strains. Immunization tests with the SY2-HA mRNA-LNP vaccine were repeated in the SPF chicken model, inducing antibody production levels that are consistent with previous tests and providing 100% complete protection against both homologous and heterologous strains of the virus, indicating that the vaccine has a stable immune efficacy.

Conclusions: The vaccine developed in this study provides complete protection against divergent H5N1 AIV strains in chickens, offering a promising approach for the future development of mRNA vaccines against multivalent avian influenza subtypes.

References
1.
Muronetz V, Barinova K, Stroylova Y, Semenyuk P, Schmalhausen E . Glyceraldehyde-3-phosphate dehydrogenase: Aggregation mechanisms and impact on amyloid neurodegenerative diseases. Int J Biol Macromol. 2016; 100:55-66. DOI: 10.1016/j.ijbiomac.2016.05.066. View

2.
Chen X, Liu S, Goraya M, Maarouf M, Huang S, Chen J . Host Immune Response to Influenza A Virus Infection. Front Immunol. 2018; 9:320. PMC: 5845129. DOI: 10.3389/fimmu.2018.00320. View

3.
Nachbagauer R, Krammer F . Universal influenza virus vaccines and therapeutic antibodies. Clin Microbiol Infect. 2017; 23(4):222-228. PMC: 5389886. DOI: 10.1016/j.cmi.2017.02.009. View

4.
Li J, Liu Q, Liu J, Wu X, Lei Y, Li S . An mRNA-based rabies vaccine induces strong protective immune responses in mice and dogs. Virol J. 2022; 19(1):184. PMC: 9652961. DOI: 10.1186/s12985-022-01919-7. View

5.
Xiong F, Zhang C, Shang B, Zheng M, Wang Q, Ding Y . An mRNA-based broad-spectrum vaccine candidate confers cross-protection against heterosubtypic influenza A viruses. Emerg Microbes Infect. 2023; 12(2):2256422. PMC: 10512870. DOI: 10.1080/22221751.2023.2256422. View