Developing a Novel Mumps Virus Vaccine

描述（由申请方提供）：腮腺炎病毒（MuV）是一种副粘病毒，可引起人体急性炎症感染，累及大多数器官系统。在流行性腮腺炎病毒疫苗大规模免疫接种之前，流行性腮腺炎病毒感染是病毒性脑膜炎和脑炎的最常见原因。免疫实践咨询委员会（ACIP）在1977年建议接种单剂MuV疫苗，1989年ACIP建议将MuV疫苗增加到两剂。即使有广泛的疫苗接种计划，腮腺炎疫情仍在继续发生。美国在实施两剂MuV疫苗接种计划后最大的MuV疫情发生在2006年。这被认为是第一次两剂MuV疫苗接种失败。2010年，纽约/新泽西地区发生了大规模MuV疫情。虽然暴发的确切原因尚不清楚，但这些暴发的可能原因（不相互排斥）包括（1）免疫力减弱和（2）由于出现新的腮腺炎病毒株而导致疫苗失效。在两剂MuV疫苗覆盖率超过95%的人群中发生疫情的事实强烈表明，目前的疫苗无效。目前的疫苗是基于基因型A，而爆发是由基因型G MuV引起的。所有这些可能的原因表明，需要一种新的疫苗，是有效的对目前爆发的流行性腮腺炎病毒株。这项提案的长期目标是开发一种具有持久免疫力的新型腮腺炎病毒疫苗。我们推测，使用反向遗传学系统产生的MuV突变体是很好的疫苗候选者。我们建议开发一种新的腮腺炎病毒疫苗，通过在基因组内的理想位置引入突变来减毒病毒，并在小鼠和雪貂中测试候选疫苗的免疫原性。

DESCRIPTION (provided by applicant): Mumps virus (MuV), a paramyxovirus, causes acute inflammatory infections in humans involving most organ systems. Mumps virus infection was the most common cause of viral meningitis and encephalitis before mass immunization with the mumps virus vaccine. Advisory Committee on Immunization Practices (ACIP) recommended a single dose immunization of MuV vaccine in 1977 and in 1989 ACIP recommended to increase MuV vaccine to two doses. Even with widespread vaccination programs in place, mumps outbreaks continue to occur. The largest MuV outbreak in the US after implementation of two-dose MuV vaccination program occurred in 2006. It is considered the first failure of two-dose MuV vaccination. In 2010, a large MuV outbreak occurred in NY/NJ area. While definitive causes for the outbreaks are not known, possible reasons (not mutually exclusive) for these outbreaks include (1) waning immunity and (2) vaccine failure due to emergence of a new mumps virus strain. The fact that outbreaks had occurred in populations with over 95% coverage of two-dose MuV vaccine strongly suggests that the current vaccine is not effective. The current vaccine is based on genotype A while outbreaks were caused by genotype G MuV. All these possible causes indicate a need for a new vaccine that is effective against current outbreak strain of mumps virus. Long-term goal of this proposal is to develop a new mumps virus vaccine with long-lasting immunity. We hypothesize that MuV mutants generated using reverse genetics system are good vaccine candidates. We propose to develop a novel mumps virus vaccine by attenuating virus through introducing mutations at desirable locations within the genome and to test immunogenicity of vaccine candidates in mice and ferrets.