Development of a Cytomegalovirus Vaccine

描述（由申请人提供）：人巨细胞病毒（HCMV）是疱疹病毒家族的一员，是导致出生缺陷的主要病毒，在免疫抑制个体中引起显著的发病率和死亡率。预防巨细胞病毒（CMV）相关疾病的疫苗的需求非常大，在育龄前对妇女进行免疫接种至关重要。我们研究的主要目的是利用小鼠模型开发一种疫苗，该疫苗将提供灭菌免疫，并充分保护免受急性和潜伏的巨细胞病毒感染。策略是使用DNA疫苗接种与灭活病毒免疫相结合的技术，以确定小鼠巨细胞病毒（MCMV）基因产物的哪种组合和疫苗给药途径将对随后的肠外或粘膜病毒攻击产生最有力和最具保护性的免疫反应。我们已经完成了若干试点项目，并在实现该项目的目标方面取得了重大进展。我们最重要的成就是，我们已经开发出一种疫苗方法，可以完全保护BALB/c小鼠免受随后的毒性病毒全身感染。在本次拨款申请中，我们建议实现以下3个目标：1。确定双重免疫对粘膜攻击的保护效果；2. 确定DNA免疫途径是否影响保护作用；和3。优化疫苗接种方案。这项研究的长期目标是阐明成功接种疫苗的基本原则，并将这些信息应用于人类疫苗的开发。

DESCRIPTION (provided by applicant): 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.