Developing a Novel Mumps Virus Vaccine

描述(申请人提供)：腮腺炎病毒(MUV)是一种副粘病毒，可引起人类急性炎症性感染，涉及大多数器官系统。在大规模接种腮腺炎病毒疫苗之前，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)于1977年建议对MIV疫苗进行单剂免疫，1989年ACIP建议将MIV疫苗增加到两剂。即使有了广泛的疫苗接种计划，腮腺炎疫情仍在继续发生。美国实施两剂MIV疫苗接种计划后最大规模的MUV疫情发生在2006年。这被认为是两剂MIV疫苗接种的第一次失败。2010年，纽约/新泽西州地区发生了一次大规模的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(不是相互排斥的)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败。暴发发生在两剂MUV疫苗覆盖率超过95%的人群中，这一事实有力地表明，目前的疫苗是无效的。目前的疫苗是基于A基因的，而暴发是由G-Muv基因引起的。所有这些可能的原因表明，需要一种新的疫苗，对目前暴发的腮腺炎病毒株有效。这项提议的长期目标是开发一种新的具有持久免疫力的腮腺炎病毒疫苗。我们推测，使用反向遗传学系统产生的Muv突变体是很好的候选疫苗。我们建议开发一种新的腮腺炎病毒疫苗，通过在基因组中合适的位置引入突变来减毒病毒，并在小鼠和雪貂身上测试候选疫苗的免疫原性。 公共卫生相关性：目前基于A基因的流行性腮腺炎病毒疫苗(JL株)已经使用了40多年。最近，在接种疫苗的人群中发生大规模疫情的频率越来越高。流行性腮腺炎病毒(G型)感染在接种疫苗人群中的暴发突显了开发一种新的有效疫苗对抗目前暴发的流行性腮腺炎病毒(G型)的紧迫性和重要性。

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. PUBLIC HEALTH RELEVANCE: Current mumps virus vaccine (JL strain) based on genotype A has been used for over 40 years. Recently, large outbreaks in vaccinated populations have occurred at increasing frequency. The outbreaks of mumps virus (genotype G) infection in vaccinated populations underscore the urgency and importance of developing a new and effective vaccine against mumps virus (genotype G) that caused current outbreaks.