Development of a Cytomegalovirus Vaccine

人类巨细胞病毒（HCMV）是疱疹病毒家族的成员，是导致人类巨细胞病毒性肺炎的主要病毒原因。 出生缺陷并导致免疫抑制个体的显著发病率和死亡率。有一个 对预防巨细胞病毒（CMV）相关疾病的疫苗的巨大需求， 在达到生育年龄之前对妇女进行免疫至关重要。主要 我们的研究目的是利用小鼠模型开发一种疫苗， 免疫力和保护充分防止急性和潜伏CMV感染。策略是使用 DNA疫苗接种与灭活病毒免疫相结合的技术，以确定 鼠巨细胞病毒（MCMV）基因产物和疫苗施用途径的组合 将产生最有力的和保护性的免疫反应，以对抗随后的胃肠外或 粘膜病毒攻击。我们已经完成了一些试点项目，并取得了重大进展。 实现该项目目标的进展情况。我们最重要的成就是 开发了一种疫苗方法，完全保护BALB/c小鼠免受随后的全身感染 致命的病毒在这项资助申请中，我们建议实现以下三个目标：1。确定 针对粘膜攻击的双重免疫的保护功效; 2.确定是否 DNA免疫途径影响保护力; 3.优化疫苗接种方案。远程 本研究的目的是阐明成功接种疫苗的基本原则，并将其应用于 为开发人类疫苗提供信息。

Human cytomegalovirus (HCMV), a member of the herepesvirus family, is the leading viral cause of birth defects and causes significant morbidity and mortality in immunosuppressed individuals. There is a great need for vaccines that will prevent cytomegalovirus (CMV) associated disease, with the immunization of women before reaching childbearing age being of paramount importance. The major objective of our research is to utilize the murine model to develop a vaccine that will provide sterilizing immuniity and protect fully against both the acute and latent CMV infection. The strategy is to use the technique of DNA vaccination coupled with immunization with inactivated virus to determine which combination of murine cytomegalovirus (MCMV) gene products and route of administration of vaccine will generate the most vigorous and protective immune response against a subsequent parenteral or mucosal viral challenge. We have already completed a number of pilot projects and have made significant progress towards achieving the goals of this project. Our most important accomplishment is that we have developed a vaccine approach that completely protects BALB/c mice from subsequent systemic infection with virulent virus. In this grant application, we propose to accomplish the following 3 aims: 1. Determine the protective efficacy of the dual immunization against mucosal challenge; 2. Determine whether the route of DNA immunization affects protection; and 3. Optimize the vaccination protocol. The long range goals of this research are to elucidate the underlying principles of successful vaccination and apply this information towards the development of a human vaccine.