Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Virology. 2011 Aug 15;417(1):196-202. doi: 10.1016/j.virol.2011.05.014. Epub 2011 Jun 30.
Low pH treatment of influenza virus hemagglutinin (HA) exposes its relatively conserved stalk domain, suggesting a potential immunogen with capability to induce broader immune responses. Here, we describe characterization, immunogenicity, antigenicity, and protective immunity induced by low pH treated inactivated whole viral vaccine in comparison with the untreated vaccine. The acidic pH treated viral vaccine showed high susceptibility to proteolytic cleavage and low hemagglutination activity indicating conformational changes. Immunization of mice with low pH treated viral vaccine induced lower levels of homologous or heterologous virus-specific binding and neutralizing antibodies compared to the untreated vaccine. Also, low pH treated influenza viral antigen showed lower antigenicity compared to the untreated influenza viral antigen. Lower efficacy of cross-protection against heterosubtypic virus was observed in the low-pH treated vaccine group. The results provide evidence that there is a correlation between protective efficacy and the stability of vaccines.
低 pH 值处理流感病毒血凝素(HA)会暴露出其相对保守的茎干结构域,这表明其具有作为潜在免疫原的能力,能够诱导更广泛的免疫反应。在此,我们描述了低 pH 值处理灭活全病毒疫苗的特性、免疫原性、抗原性和诱导的保护免疫,将其与未经处理的疫苗进行了比较。酸性 pH 值处理的病毒疫苗表现出对蛋白水解切割的高敏感性和低血凝活性,表明其构象发生了变化。与未经处理的疫苗相比,用低 pH 值处理的病毒疫苗免疫的小鼠产生的同源或异源病毒特异性结合和中和抗体水平较低。此外,与未经处理的流感病毒抗原相比,低 pH 值处理的流感病毒抗原的抗原性较低。在低 pH 值处理疫苗组中,观察到针对异源病毒的交叉保护效果较低。这些结果提供了证据表明,保护效力与疫苗的稳定性之间存在相关性。