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

作者：Zhaoyang Wang, Chongyu Tian, Junyu Zhu, Shiqian Wang, Xiang Ao, Yanjuan He, Huixin Chen, Xiuying Liao, De‐Ming Kong, Yong-Fei Zhou, Wanbo Tai, Ming Liao, Huiying Fan · 发表于：Journal of Nanobiotechnology · 年份：2025 · DOI：10.1186/s12951-025-03156-w · 被引用次数：13 · 研究领域：Influenza Virus Research Studies、Animal Disease Management and Epidemiology、Virus-based gene therapy research

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 consi...