Development of a Cytomegalovirus Vaccine

描述(申请人提供)：人类巨细胞病毒(HCMV)是疱疹病毒家族的成员，是导致出生缺陷的主要病毒原因，并在免疫抑制患者中导致显著的发病率和死亡率。非常需要预防巨细胞病毒(CMV)相关疾病的疫苗，最重要的是在育龄前为妇女接种疫苗。我们研究的主要目标是利用小鼠模型开发一种疫苗，该疫苗将提供灭菌免疫力，并完全预防急性和潜伏的CMV感染。该策略是使用DNA疫苗和灭活病毒免疫相结合的技术来确定哪种小鼠巨细胞病毒(MCMV)基因产物和疫苗接种途径的组合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。我们已经完成了一些试点项目，并在实现这一项目的目标方面取得了重大进展。我们最重要的成就是，我们开发了一种疫苗方法，完全保护BALB/c小鼠免受随后的全身毒力病毒感染。在本次拨款申请中，我们建议完成以下三个目标：1.确定双重免疫对黏膜攻击的保护效果；2.确定DNA免疫途径是否影响保护；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理，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.