Avian Influenza Virus Vaccines Bearing Immunomodulators

描述（由申请方提供）：禽流感病毒对发展中国家和发达国家的人和鸡的健康构成重大威胁。鸡和水生鸟类也是流感病毒的储存库，在过去几年中，这些病毒越来越多地越过禽-人屏障，在几个大陆的人类中引起致命疾病。这一宿主作为大流行性流感病毒株的潜在来源而引起重大关切。灭活疫苗目前可用于保护免受一些流行菌株的侵害，并且对于这些菌株，疫苗可有效预防疾病。然而，这些疫苗不能完全防止病毒脱落。现有灭活疫苗的另一个重要问题是，它们对不同的流感病毒株提供最低限度的交叉保护。灭活疫苗诱导的保护作用是由抗病毒血凝素和神经氨酸酶的抗体介导的。这些蛋白质的抗原表位的微小变化，称为“抗原漂移”，可严重降低疫苗效力。已经在哺乳动物中进行了令人鼓舞的努力，使用补充有细胞因子的灭活疫苗诱导T细胞毒性和Th 1型应答，因为这些应答对流感的同型和异型株更有效。然而，这些努力并不容易转化为商业上可行的禽流感疫苗的生产。为了解决这个问题，我们提出了一种分子方法，将锚鸡免疫调节细胞因子和趋化因子的包膜糖蛋白的流感病毒。病毒将通过保留附着分子完整生物活性的方案完全灭活。我们的假设是，细胞因子或趋化因子修饰的病毒颗粒将诱导有效的Th 1和/或T细胞毒性反应，除了保护性体液反应，因此，提供更好的保护，对同型和异型流感毒株。

DESCRIPTION (provided by applicant): Avian influenza viruses pose a significant health threat for both humans and chickens in developing and developed countries. Chickens and aquatic avian species also provide a reservoir of influenza viruses that have increasingly in the last several years crossed the avian-human barrier and caused fatal disease in humans across several continents. This reservoir is of major concern as a potential source of pandemic influenza virus strains. Inactivated vaccines are currently available for protection against some of the circulating strains, and for these strains the vaccines are effective in preventing disease. However, these vaccines do not completely prevent viral shedding. Another significant problem with existing killed vaccines is that they confer minimal cross-protection to divergent influenza strains. Protection induced by inactivated vaccines is mediated by antibody to the viral hemagglutinin and neuraminidase. Minor changes in antigenic epitopes of these proteins, termed "antigenic drift" can severely reduce vaccine efficacy. Encouraging efforts have been made in mammals to induce T cytotoxic and Th 1 type responses using killed vaccines supplemented with cytokines, since these responses are more efficacious against homotypic and heterotypic strains of influenza. However, these efforts are not easily translated to the production of commercially feasible avian vaccines. To address this problem, we are proposing a molecular approach that will anchor chicken immunomodulatory cytokines and chemokines to the envelope glycoproteins of influenza virus. The viruses will be completely inactivated with a protocol that leaves the bioactivity of the attached molecule intact. Our hypothesis is that cytokine- or chemokine-modified virus particles will induce an efficacious Th1 and/or T cytotoxic responses in addition to a protective humoral response and thus, provide better protection against homotypic and heterotypic influenza strains.