Sownthirarajan Boopathi, Mason Maya, Loganathan Gayathri, Manivasagam Senthamizharasi, Jangra Rohit K, Tan Gene S, Perez Daniel R, Manicassamy Balaji
Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA.
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, USA.
J Virol. 2025 Sep 23;99(9):e0097525. doi: 10.1128/jvi.00975-25. Epub 2025 Aug 8.
The H5N1 strain of influenza A virus (IAV) continues to cause severe infections in a range of avian and mammalian species, including sporadic but concerning cases in humans. There is growing concern that circulating H5N1 strains could lead to widespread human outbreaks. Research with highly pathogenic H5N1 viruses is restricted to Biosafety Level 3 (BSL-3) laboratories. Vesicular stomatitis virus (VSV)-based vaccine vectors expressing heterologous viral proteins from Ebola, SARS-CoV-2, Lassa virus, etc., have previously been shown to be safe and effective in animal models and human clinical trials. Here, we report the development of a recombinant VSV expressing the hemagglutinin (HA) and neuraminidase (NA) genes of H5N1 IAV (H5N1-VSV), which serves as a versatile platform to study various aspects of H5N1 IAV biology. H5N1-VSV replicated robustly to titers comparable to those of the full H5N1 virus in multiple cell lines. In mice, H5N1-VSV vaccination was safe, elicited strong immunity, and conferred protection against a circulating H5N1 strain. Notably, we found that polymorphisms in antigenic site Sa of circulating strains emerged under immune selection pressure in cattle, resembling the evolution of pandemic IAV in humans. These findings suggest that H5N1-VSV can serve as a safe, adaptable platform for influenza research.
甲型流感病毒（IAV）的H5N1毒株继续在一系列禽类和哺乳动物物种中引发严重感染，包括人类中的散发病例，但令人担忧。人们越来越担心，正在传播的H5N1毒株可能导致大规模的人类疫情爆发。对高致病性H5N1病毒的研究仅限于生物安全3级（BSL-3）实验室。基于水疱性口炎病毒（VSV）的疫苗载体表达来自埃博拉病毒、SARS-CoV-2、拉沙病毒等的异源病毒蛋白，此前已在动物模型和人类临床试验中证明是安全有效的。在此，我们报告了一种表达H5N1 IAV血凝素（HA）和神经氨酸酶（NA）基因的重组VSV（H5N1-VSV）的开发，它作为一个通用平台，用于研究H5N1 IAV生物学的各个方面。H5N1-VSV在多种细胞系中能强劲复制，滴度与完整H5N1病毒相当。在小鼠中，H5N1-VSV疫苗接种是安全的，能引发强大的免疫力，并能抵御正在传播的H5N1毒株。值得注意的是，我们发现，循环毒株抗原位点Sa的多态性在牛的免疫选择压力下出现，类似于人类大流行性IAV的进化。这些发现表明，H5N1-VSV可作为流感研究的一个安全、适应性强的平台。
