Avian Influenza Virus Vaccines Bearing Immunomodulators

含有免疫调节剂的禽流感病毒疫苗

• 批准号: 7093718
• 负责人: P. CHRIS ROBERTS
• 金额: $ 6.13万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7093718
• 关键词: chemokine; chickens; cytokine; disease outbreaks; human; immunomodulators; influenza

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.

描述（由申请人提供）：禽流感病毒对发展中国家和发达国家的人类和鸡构成重大健康威胁。鸡和水生鸟类也提供了流感病毒的储存库，这些病毒在过去几年中越来越多地跨越了禽-人的屏障，并在几个大陆上造成人类致命疾病。作为大流行性流感病毒毒株的潜在来源，这一水库引起了重大关注。目前有灭活疫苗可用于预防某些流行毒株，对于这些毒株，疫苗可有效预防疾病。然而，这些疫苗并不能完全阻止病毒的脱落。现有灭活疫苗的另一个重大问题是，它们对不同流感毒株的交叉保护作用很小。灭活疫苗诱导的保护作用是由病毒血凝素和神经氨酸酶抗体介导的。这些蛋白抗原表位的微小变化，称为“抗原漂移”，可严重降低疫苗效力。在哺乳动物中已经取得了令人鼓舞的努力，利用补充细胞因子的灭活疫苗诱导T细胞毒性和Th 1型反应，因为这些反应对同型和异型流感毒株更有效。然而，这些努力并不容易转化为生产商业上可行的禽流感疫苗。为了解决这个问题，我们提出了一种分子方法，将鸡的免疫调节细胞因子和趋化因子锚定在流感病毒的包膜糖蛋白上。病毒将被完全灭活，其程序将使附着分子的生物活性保持不变。我们的假设是，细胞因子或趋化因子修饰的病毒颗粒除了保护性体液反应外，还会诱导有效的Th1和/或T细胞毒性反应，从而提供更好的保护，抵御同型和异型流感毒株。