Developing a Novel Mumps Virus Vaccine

开发新型腮腺炎病毒疫苗

• 批准号: 8650782
• 负责人: Biao He
• 金额: $ 37.13万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-10 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8650782
• 关键词: 5 year old; Acute; Advisory Committees; Animal Model; Animals; Area; Attenuated; Attenuated Live Virus Vaccine; Attenuated Vaccines; Cell Line; Child; Clinical; Clinical Trials; Disease; Disease Outbreaks; Dose; Failure; Ferrets; Frequencies; Genome; Genotype; Goals; Human; Human Virus; Immunity; Immunization; Infection; Inflammatory; Life; Location; Lung; Mass Immunization; Measles-Mumps-Rubella Vaccine; Modeling; Morphology; Mumps; Mumps virus; Mus; Mutate; Mutation; Paramyxovirus; Pathogenesis; Physiology; Point Mutation; Population; Rattus; Recombinants; Regimen; Safety; System; Testing; Vaccinated; Vaccination; Vaccine Production; Vaccines; Vero Cells; Viral Encephalitis; Viral Genome; Viral meningitis; Virus; Virus Diseases; base; body system; immunogenicity; improved; mouse model; mutant; neurotoxicity; novel; novel vaccines; pathogen; positional cloning; programs; recombinant virus; respiratory; respiratory virus; tissue/cell culture; vaccine candidate

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.

描述（由申请人提供）：腮腺炎病毒（MuV）是一种副粘病毒，会引起人类大多数器官系统的急性炎症感染。在使用腮腺炎病毒疫苗进行大规模免疫之前，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 MuV 疫苗进行单剂量免疫，并于 1989 年建议将 MuV 疫苗增加到两剂。即使实施了广泛的疫苗接种计划，腮腺炎疫情仍然持续发生。 2006年，美国实施两剂MuV疫苗接种计划后最大规模的MuV疫情爆发，被认为是两剂MuV疫苗接种的首次失败。 2010年，纽约/新泽西地区发生大规模MuV爆发。虽然爆发的确切原因尚不清楚，但这些爆发的可能原因（并不相互排斥）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败。两剂 MuV 疫苗覆盖率超过 95% 的人群中爆发疫情的事实强烈表明，当前的疫苗无效。目前的疫苗是基于 A 基因型，而疫情则是由 G 基因型 MuV 引起的。所有这些可能的原因表明需要一种能有效对抗当前爆发的流行性腮腺炎病毒株的新疫苗。该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。我们假设使用反向遗传学系统产生的 MuV 突变体是良好的候选疫苗。我们建议通过在基因组内的所需位置引入突变来减毒病毒，从而开发一种新型腮腺炎病毒疫苗，并在小鼠和雪貂中测试候选疫苗的免疫原性。