Developing a Novel Mumps Virus Vaccine

开发新型腮腺炎病毒疫苗

基本信息

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
项目类别：
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

项目摘要

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）：斑疹病毒（MUV），一种帕托氏病毒，会引起涉及大多数器官系统的人类的急性炎症感染。腮腺炎病毒感染是病毒性脑膜炎和脑炎的最常见原因，然后用腮腺炎病毒疫苗进行质量免疫。免疫实践咨询委员会（ACIP）建议1977年对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。即使制定了广泛的疫苗接种计划，腮腺炎爆发仍在继续。实施两剂量MUV疫苗接种计划后，美国最大的MUV暴发发生在2006年。这被认为是两剂量MUV疫苗接种的第一次失败。 2010年，纽约州/NJ地区发生了一次大型MUV爆发。尽管未知暴发的确切原因，但这些暴发的可能原因（不是相互排斥）包括（1）由于出现了新的腮腺炎病毒菌株而导致的疫苗衰竭和（2）疫苗失败。在两剂量MUV疫苗覆盖率以上超过95％的人群中发生了暴发的事实，强烈表明当前的疫苗无效。当前的疫苗基于基因型A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，该疫苗有效地抵抗腮腺炎病毒的当前爆发菌株。该提议的长期目标是开发具有长期免疫力的新的腮腺炎病毒疫苗。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理想的位置引入突变并测试小鼠和雪貂疫苗候选物的免疫原性，从而开发一种新型的腮腺炎病毒疫苗。