Department of Biomedical Engineering, Watson School of Engineering and Applied Sciences, Binghamton University, State University of New York (SUNY), Binghamton, NY 13902, USA.
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
J Immunol Res. 2016;2016:4131324. doi: 10.1155/2016/4131324. Epub 2016 Dec 19.
Highly pathogenic H5N1 avian influenza viruses pose a pandemic threat to human health. A rapid vaccine production against fast outbreak is desired. We report, herein, a paradigm-shift influenza vaccine technology by presenting H5N1 hemagglutinin (HA) to the surface of yeast. We demonstrated, for the first time, that the HA surface-presented yeast can be used as influenza vaccines to elicit both humoral and cell-mediated immunity in mice. The HI titer of antisera reached up to 128 in vaccinated mice. A high level of H5N1 HA-specific IgG1 and IgG2a antibody production was detected after boost immunization. Furthermore, we demonstrated that the yeast surface-displayed HA preserves its antigenic sites. It preferentially binds to both avian- and human-type receptors. In addition, the vaccine exhibited high cross-reactivity to both homologous and heterologous H5N1 viruses. A high level production of anti-HA antibodies was detected in the mice five months after vaccination. Finally, our animal experimental results indicated that the yeast vaccine offered complete protection of mice from lethal H5N1 virus challenge. No severe side effect of yeast vaccines was noted in animal studies. This new technology allows for rapid and large-scale production of influenza vaccines for prepandemic preparation.
高致病性 H5N1 禽流感病毒对人类健康构成了大流行威胁。人们希望能够快速生产针对快速爆发的疫苗。在此,我们报告了一种流感疫苗技术的范式转变,即将 H5N1 血凝素(HA)呈现在酵母表面。我们首次证明,呈现在酵母表面的 HA 可被用作流感疫苗,在小鼠中引发体液和细胞介导的免疫反应。接种疫苗的小鼠中的 HI 效价高达 128。在加强免疫后,检测到高水平的 H5N1 HA 特异性 IgG1 和 IgG2a 抗体产生。此外,我们证明酵母表面展示的 HA 保留了其抗原表位。它优先结合禽源和人源受体。此外,该疫苗对同源和异源 H5N1 病毒均表现出高交叉反应性。接种疫苗五个月后,在小鼠中检测到高水平的抗 HA 抗体产生。最后,我们的动物实验结果表明,酵母疫苗为小鼠提供了针对致死性 H5N1 病毒攻击的完全保护。在动物研究中未观察到酵母疫苗的严重副作用。这项新技术允许快速和大规模生产流感疫苗,以用于大流行前的准备。