Developing a Novel Mumps Virus Vaccine

描述（由申请人提供）：腮腺炎病毒（MuV）是一种副粘病毒，可引起人类大多数器官系统的急性炎症性感染。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年建议单剂接种MuV疫苗，1989年ACIP建议将MuV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。2006年，在实施双剂MuV疫苗接种计划后，美国发生了最大的MuV疫情。这被认为是两剂MuV疫苗接种的第一次失败。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（并非相互排斥）包括：(1)免疫力下降和(2)由于出现新的腮腺炎病毒株而导致疫苗失效。疫情发生在两剂MuV疫苗覆盖率超过95%的人群中，这一事实强烈表明，目前的疫苗并不有效。目前的疫苗是基于A基因型，而疫情是由G基因型MuV引起的。所有这些可能的原因表明，需要一种新的疫苗，对目前爆发的流行性腮腺炎病毒株有效。这项建议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。我们假设使用反向遗传系统产生的MuV突变体是良好的候选疫苗。我们建议开发一种新型腮腺炎病毒疫苗，通过在基因组内的理想位置引入突变来减毒，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. 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.