Avian influenza mRNA vaccine encoding hemagglutinin provides complete protection against divergent H5N1 viruses in specific-pathogen-free chickens

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...

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Main Authors: Zhaoyang Wang, Chongyu Tian, Jiahang Zhu, Shiqian Wang, Xiang Ao, Yanjuan He, Huixin Chen, Xiuying Liao, Deming Kong, Yongfei Zhou, Wanbo Tai, Ming Liao, Huiying Fan
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Journal of Nanobiotechnology
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Online Access:https://doi.org/10.1186/s12951-025-03156-w
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author Zhaoyang Wang
Chongyu Tian
Jiahang Zhu
Shiqian Wang
Xiang Ao
Yanjuan He
Huixin Chen
Xiuying Liao
Deming Kong
Yongfei Zhou
Wanbo Tai
Ming Liao
Huiying Fan
author_facet Zhaoyang Wang
Chongyu Tian
Jiahang Zhu
Shiqian Wang
Xiang Ao
Yanjuan He
Huixin Chen
Xiuying Liao
Deming Kong
Yongfei Zhou
Wanbo Tai
Ming Liao
Huiying Fan
author_sort Zhaoyang Wang
collection DOAJ
description 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. Graphical Abstract
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spelling doaj-art-d7a19acbaa924fdca41037c64ce246732025-02-02T12:41:01ZengBMCJournal of Nanobiotechnology1477-31552025-01-0123112010.1186/s12951-025-03156-wAvian influenza mRNA vaccine encoding hemagglutinin provides complete protection against divergent H5N1 viruses in specific-pathogen-free chickensZhaoyang Wang0Chongyu Tian1Jiahang Zhu2Shiqian Wang3Xiang Ao4Yanjuan He5Huixin Chen6Xiuying Liao7Deming Kong8Yongfei Zhou9Wanbo Tai10Ming Liao11Huiying Fan12College of Veterinary Medicine, South China Agricultural UniversityInstitute of Infectious Diseases, Shenzhen Bay LaboratoryCollege of Veterinary Medicine, South China Agricultural UniversityCollege of Veterinary Medicine, South China Agricultural UniversityCollege of Veterinary Medicine, South China Agricultural UniversityCollege of Veterinary Medicine, South China Agricultural UniversityCollege of Veterinary Medicine, South China Agricultural UniversityCollege of Veterinary Medicine, South China Agricultural UniversityCollege of Veterinary Medicine, South China Agricultural UniversityInstitute of Hemu Biotechnology, Beijing Hemu Biotechnology Co., LtdInstitute of Infectious Diseases, Shenzhen Bay LaboratoryCollege of Veterinary Medicine, South China Agricultural UniversityCollege of Veterinary Medicine, South China Agricultural UniversityAbstract 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. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03156-wH5N1HAmRNA vaccineLipid nanoparticlemRNA secondary structure
spellingShingle Zhaoyang Wang
Chongyu Tian
Jiahang Zhu
Shiqian Wang
Xiang Ao
Yanjuan He
Huixin Chen
Xiuying Liao
Deming Kong
Yongfei Zhou
Wanbo Tai
Ming Liao
Huiying Fan
Avian influenza mRNA vaccine encoding hemagglutinin provides complete protection against divergent H5N1 viruses in specific-pathogen-free chickens
Journal of Nanobiotechnology
H5N1
HA
mRNA vaccine
Lipid nanoparticle
mRNA secondary structure
title Avian influenza mRNA vaccine encoding hemagglutinin provides complete protection against divergent H5N1 viruses in specific-pathogen-free chickens
title_full Avian influenza mRNA vaccine encoding hemagglutinin provides complete protection against divergent H5N1 viruses in specific-pathogen-free chickens
title_fullStr Avian influenza mRNA vaccine encoding hemagglutinin provides complete protection against divergent H5N1 viruses in specific-pathogen-free chickens
title_full_unstemmed Avian influenza mRNA vaccine encoding hemagglutinin provides complete protection against divergent H5N1 viruses in specific-pathogen-free chickens
title_short Avian influenza mRNA vaccine encoding hemagglutinin provides complete protection against divergent H5N1 viruses in specific-pathogen-free chickens
title_sort avian influenza mrna vaccine encoding hemagglutinin provides complete protection against divergent h5n1 viruses in specific pathogen free chickens
topic H5N1
HA
mRNA vaccine
Lipid nanoparticle
mRNA secondary structure
url https://doi.org/10.1186/s12951-025-03156-w
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