CONGENITAL VIRUS INFECTION AND VACCINATION STRATEGIES FOR INFANTS

婴儿先天性病毒感染和疫苗接种策略

• 批准号: 6101165
• 负责人: K. M CARBONE
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6101165
• 关键词: active immunization; brain injury; developmental neurobiology; drug adverse effect; histopathology; laboratory rat; microorganism culture; mumps virus; neurotropic virus; newborn animals; viral vaccines; virulence

Congenital brain damage due to intrauterine virus infections is a significant pediatric problem. In addition, the brain continues to develop during the first year of postnatal life. Since the developing nervous system is uniquely sensitive to damage following virus infection, administering neurovirulent vaccines to infants can place the child~s nervous system at increased risk for vaccine related injury. Mumps virus, and certain strains of mumps vaccine (Urabe Am9, Leningrad 3), are among the most neurotropic of the early childhood viruses, and new MMR combinations continue to be proposed, including new strains of mumps vaccine virus. Neurovirulence safety tests (NVST) are needed to identify neurovirulent vaccines that may cause CNS disease following vaccination. Progress: NSVT Development: Primate: Developed and tested a simplified, biologically relevant, standardized primate NVST. Animals inoculated with wild type and vaccine strains of mumps virus developed inflammation. Licensed mumps vaccine was statistically no different from experimental mumps vaccine. The test was unable to differentiate vaccine from wild type strains at a single dose; thus additional studies are underway to evaluate the "dose response" curve for each virus re: ability to induce neurological damage. In addition, we are developing, testing and validating virus and immune serum standards for assistance in uniform execution of primate NVST by regulatory agencies and sponsors. Small animal: A newborn rat NVST was developed and tested with neurovirulent (Kilham) and relatively non-neurovirulent (Jeryl-Lynn) strains of mumps viruses. Using physiological, neuroanatomical and behavioral endpoints, significant differences were identified in rats infected at birth with Kilham or Jeryl-Lynn viruses. These results are In Press in J. Virology, 1998. Additional experiments are underway to complete validation of this model system and to evaluate a dose-response curve for neurovirulence induction by wild type and vaccine mumps virus strains.

由于宫内病毒感染引起的先天性脑损伤是一种 严重的儿科问题 此外，大脑继续 在出生后的第一年发育。由于显影 神经系统对病毒感染后的损伤特别敏感， 给婴儿接种神经毒性疫苗可使儿童的免疫力下降。 神经系统疫苗相关损伤的风险增加。 腮腺炎 病毒和某些腮腺炎疫苗株（Urabe Am 9，Leningrad 3）， 其中最神经嗜性的幼儿病毒，和新的MMR 继续提出组合，包括腮腺炎的新菌株， 疫苗病毒 神经毒力安全性测试（NVST）需要识别 神经毒力疫苗接种后可能导致CNS疾病。 进展：NSVT开发：灵长类动物：开发和测试了一个 简化的、生物学相关的、标准化的灵长类NVST。 动物 接种野生型和疫苗株腮腺炎病毒开发 炎症许可的腮腺炎疫苗在统计上与 实验性腮腺炎疫苗 该测试无法区分疫苗 从野生型菌株在单一剂量;因此，额外的研究是 目前正在评估每种病毒的“剂量反应”曲线， 导致神经损伤的能力。 此外，我们正在开发， 测试和验证病毒和免疫血清标准品，以提供帮助 监管机构和申办者统一执行灵长类动物NVST。 小动物：开发了新生大鼠NVST，并使用 神经毒性（Kilham）和相对非神经毒性（Jeryl-Lynn） 腮腺炎病毒株。 利用生理学、神经解剖学和 行为终点，在大鼠中确定了显著差异 在出生时感染了Kilham或Jeryl-Lynn病毒。 这些结果 出版于J. Virology，1998年。 其他实验正在进行中， 完整验证该模型系统，并评估剂量反应 野生型和疫苗腮腺炎病毒的神经毒力诱导曲线 菌株