Lee Yu-Na, Hwang Hye Suk, Kim Min-Chul, Lee Young-Tae, Lee Jong Seok, Moore Martin L, Kang Sang-Moo
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
Antiviral Res. 2015 Mar;115:1-8. doi: 10.1016/j.antiviral.2014.12.009. Epub 2014 Dec 13.
Respiratory syncytial virus (RSV) is the leading cause of viral bronchiolitis in both children and the elderly. There is no vaccine available for the prevention of RSV infection. Here, we generated recombinant influenza virus (PR8/RSV.HA-F) expressing an RSV F243-294 neutralizing epitope in the hemagglutinin (HA) as a chimeric protein. Neutralizing antibodies specific for both RSV and influenza virus were induced by a single intranasal immunization of mice with PR8/RSV.HA-F. Mice that were immunized with PR8/RSV.HA-F were protected against RSV infection comparable with live RSV as evidenced by significant reduction of RSV lung viral loads, as well as the absence of lung eosinophilia and RSV-specific cellular immune responses. In contrast, formalin-inactivated RSV-immunized mice showed severe disease and high cellular immune responses in lungs after RSV infection. These findings support a concept that recombinant influenza virus carrying the RSV F243-294 neutralizing epitope can be developed as a promising RSV vaccine candidate which induces protective neutralizing antibodies but avoids lung immunopathology.
呼吸道合胞病毒（RSV）是儿童和老年人病毒性细支气管炎的主要病因。目前尚无预防RSV感染的疫苗。在此，我们构建了重组流感病毒（PR8/RSV.HA-F），该病毒在血凝素（HA）中表达RSV F243-294中和表位作为嵌合蛋白。通过用PR8/RSV.HA-F对小鼠进行单次鼻内免疫，诱导了针对RSV和流感病毒的中和抗体。用PR8/RSV.HA-F免疫的小鼠对RSV感染具有保护作用，与活RSV相当，这表现为RSV肺病毒载量显著降低，以及肺部无嗜酸性粒细胞增多和RSV特异性细胞免疫反应。相比之下，经福尔马林灭活的RSV免疫的小鼠在RSV感染后肺部出现严重疾病和高细胞免疫反应。这些发现支持了这样一个概念，即携带RSV F243-294中和表位的重组流感病毒可以开发成为一种有前景的RSV疫苗候选物，它能诱导保护性中和抗体，但避免肺部免疫病理学。
