TESTING MUCOSAL VACCINES IN AN ANIMAL MEASLES MODEL

如果给予适当的疫苗，麻疹是一种可以根除的疾病。问题 固定和活病毒疫苗都引起了人们对新疫苗的兴趣 麻疹疫苗接种方法。新疫苗应在以下情况下有效 在母体抗体存在的情况下注射，因为早期 在流行环境中，免疫接种是必不可少的。障碍(也许更多 虚幻的)来测试新的疫苗策略 灵长类，实验动物在以下情况下不会患上麻疹样疾病 接种了麻疹病毒。然而，犬瘟热病毒(CDV)是一种 麻疹病毒，因此是麻疹病毒的近亲，确实产生一种 在雪貂中发生麻疹样感染，CDV的自然宿主：CDV通过 同样的路线，感染相同的目标细胞，导致类似的 传播性疾病，预防再次感染由 用相同的病毒结构蛋白免疫(融合[F]和 血凝素[HA]蛋白)，如麻疹。此外，年轻的雪貂 自然会受到母体抗体的保护，免受CDV感染。在……里面 简而言之，CDV是测试新的麻疹病毒疫苗的理想模型 战略。我们的长期目标是开发一种有效的麻疹疫苗 这对所有年龄段的人来说都是安全的。我们将发展 适用于粘膜和肠外的CDV候选疫苗 使用HA、F和N蛋白给药。粘膜路线将是 探索一种避免母源抗体抑制作用的方法。 我们将为此开发重组牛痘病毒。我们会 肠外和粘膜亲和层析纯化F和HA 以霍乱毒素结合亚单位(CTB)为靶标给药 佐剂，并用于制备ISCOM。然后我们将确定 这些候选疫苗在免疫幼稚人群中的保护效果 在受到母源抗体保护的雪貂和幼年雪貂中。这个 将评估粘膜和血清抗体对保护的贡献 通过检测总的、HA和F特异性的血清和分泌抗体， 病毒中和和融合抑制。我们还将确定F-， HA和N特异性雪貂抗体将增强雪貂的感染 体外巨噬细胞，CDV在体内的主要靶细胞，因为这样 加强接种可能会影响疫苗接种策略，并可能是一个因素 在服用福尔马林后非典型麻疹的发展过程中- 修正了麻疹疫苗。

Measles, given the appropriate vaccine, is an eradicable disease. Problems with both fixed and live-virus vaccines have created interest in new approaches to measles vaccination. New vaccines should be effective when administered in the presence of maternal antibody because early immunization is essential in endemic settings. An impediment (perhaps more illusory than real) to testing new vaccine strategies has been that non- primate, laboratory animals do not develop a measles-like illness when inoculated with measles virus. However, canine distemper virus (CDV), a morbillivirus and thus a close relative of measles virus, does produce a measles-like infection in ferrets, a natural host of CDV: CDV is spread by the same route, infects the same target cells, causes a similar disseminated disease, and protection against reinfection is conferred by immunization with the same virus structural proteins (the fusion [F] and hemagglutinin [HA] proteins) as with measles. In addition, young ferrets are naturally protected against CDV infection by maternal antibody. In short, CDV is an ideal model for testing new morbillivirus vaccine strategies. Our long-term goal is to develop an effective measles vaccine that can be safely administered to all age groups. We will develop candidate vaccines for CDV suitable for mucosal and parenteral administration using the HA, F and N proteins. The mucosal route will be explored as a means to avoid the inhibitory effects of maternal antibody. We will develop recombinant vaccinia viruses for this purpose. We will also purify F and HA by affinity chromatography for parenteral and mucosal administration with the cholera-toxin binding-subunit (CTB) as an adjuvant, and for preparation of ISCOMs. We will then determine the protective efficacy of these candidate vaccines in immunologically naive ferrets and in infant ferrets protected by maternal antibody. The contribution of mucosal and serum antibody to protection will be assessed by measuring total, HA- and F-specific serum and secretory antibody, virus-neutralization and fusion inhibition. We will also determine if F-, HA- and N-specific ferret antibodies will enhance infection of ferret macrophages in vitro, a principal target cell of CDV in vivo, because such enhancement could affect vaccination strategy and may have been a factor in the development of atypical measles after administration of formalin- fixed measles vaccines.