tetano
Editor, Senior Moderator
J Nanobiotechnology
. 2025 Jan 29;23(1):55.
doi: 10.1186/s12951-025-03156-w. Avian influenza mRNA vaccine encoding hemagglutinin provides complete protection against divergent H5N1 viruses in specific-pathogen-free chickens
Zhaoyang Wang[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Chongyu Tian[SUP] #[/SUP][SUP] 4 [/SUP], Jiahang Zhu[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Shiqian Wang[SUP] 1 2 3 [/SUP], Xiang Ao[SUP] 1 2 3 [/SUP], Yanjuan He[SUP] 1 2 3 [/SUP], Huixin Chen[SUP] 1 2 3 [/SUP], Xiuying Liao[SUP] 1 2 3 [/SUP], Deming Kong[SUP] 1 2 3 [/SUP], Yongfei Zhou[SUP] 5 [/SUP], Wanbo Tai[SUP] 6 [/SUP], Ming Liao[SUP] 7 8 9 [/SUP], Huiying Fan[SUP] 10 11 12 [/SUP]
Affiliations
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.
Keywords: H5N1; HA; Lipid nanoparticle; mRNA secondary structure; mRNA vaccine.
. 2025 Jan 29;23(1):55.
doi: 10.1186/s12951-025-03156-w. Avian influenza mRNA vaccine encoding hemagglutinin provides complete protection against divergent H5N1 viruses in specific-pathogen-free chickens
Zhaoyang Wang[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Chongyu Tian[SUP] #[/SUP][SUP] 4 [/SUP], Jiahang Zhu[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Shiqian Wang[SUP] 1 2 3 [/SUP], Xiang Ao[SUP] 1 2 3 [/SUP], Yanjuan He[SUP] 1 2 3 [/SUP], Huixin Chen[SUP] 1 2 3 [/SUP], Xiuying Liao[SUP] 1 2 3 [/SUP], Deming Kong[SUP] 1 2 3 [/SUP], Yongfei Zhou[SUP] 5 [/SUP], Wanbo Tai[SUP] 6 [/SUP], Ming Liao[SUP] 7 8 9 [/SUP], Huiying Fan[SUP] 10 11 12 [/SUP]
Affiliations
- PMID: 39881325
- PMCID: PMC11776166
- DOI: 10.1186/s12951-025-03156-w
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.
Keywords: H5N1; HA; Lipid nanoparticle; mRNA secondary structure; mRNA vaccine.