Equine Infectious Anemia Virus Envelope Variation and Vaccine Efficacy

马传染性贫血病毒包膜变异和疫苗功效

• 批准号: 7162506
• 负责人: Ronald C Montelaro
• 金额: $ 59.59万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-30 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7162506
• 关键词: AIDS Vaccines; AIDS vaccine development; Address; Affect; Animals; Antigen Presentation; Antigens; Attenuated; Biological; Brazil; Development; Disease; Equine Infectious Anemia; Equine Infectious Anemia Virus; Equus caballus; Evaluation; Face; France; Genes; Goals; Grant; HIV-1; Human; Immune; Immune response; Immune system; Immunity; Immunization; Immunologics; Immunophenotyping; Infection; Interdisciplinary Study; Methods; Modeling; Nature; Pennsylvania; Personal Satisfaction; Phenotype; Population; Procedures; Property; Research Design; Role; Specificity; Subfamily lentivirinae; System; Testing; Time; Vaccines; Variant; Viral Vector; Virulent; Virus; base; design; env Gene Products; immunogenic; immunogenicity; insight; novel; programs; vaccine efficacy; vector vaccine; virus envelope

DESCRIPTION (provided by applicant): We have during the past twenty years developed a comprehensive multidisciplinary research program using the equine infectious anemia virus (EIAV) system to examine the fundamental mechanisms by which lentiviruses persist despite robust host immune responses, the nature of protective and enhancing virus-specific immunity, and the evaluation of experimental immunization strategies as models for HIV-1/AIDSvaccine development. While Lentivirus envelope variation is well documented, the impact of this variation on vaccine efficacy remains largely speculative at this time. In the current application we propose to examine the hypothesis that the EIAV Env is the primary determinant of vaccine efficacy and that effective vaccines must elicit appropriate humoral and cellular immune responses to conerved immunorecessive Env determinants to provide enduring broadly protective immunity. Moreover, we suggest that both the nature of the Env immunogen and its method of presentation affect vaccine immune specificity and efficacy and that both parameters must be optimized. Thus, the following specific aims are proposed: (i) To define the humoral and cellular immune determinants of Env proteins of geographically diverse primary isolates and to assess the effects of defined sequence variation on immunogenic and antigenic properties; (ii) To examine directly the role of defined primary envelope variations on protection by experimental EIAV vaccines previously shown to be protective to homologous virus challenge; and (iii) To develop and evaluate novel immunization strategies using VEE and AAV viral vectors to elicit enduring broadly protective vaccine immunity to diverse EIAV challenge. It is anticipated that the results of the proposed studies will provide novel insights into the impact of defined natural Env variation on immune phenotypes, the relationship of challenge Env variation to vaccine efficacy, and the potential for viral vector vaccines to achieve protective immunity. Thus, the results of these EIAV studies should be complementary to ongoing vaccine studies in other animal lentivirus systems and relevant to the design and evaluation candidate human AIDS vaccines.

描述(申请人提供)：在过去的二十年里，我们使用马传染性贫血病毒(EIAV)系统开发了一个综合的多学科研究计划，以检查慢病毒在宿主免疫反应强劲的情况下仍然存在的基本机制，保护和增强病毒特异性免疫的性质，以及作为HIV-1/艾滋病疫苗开发模型的实验免疫策略的评估。虽然慢病毒包膜变异已经有了很好的记录，但这种变异对疫苗效力的影响目前仍在很大程度上是推测的。在目前的应用中，我们建议检验这样一种假设，即EIAV Env是疫苗效力的主要决定因素，有效的疫苗必须对保留的免疫隐性Env决定因素诱导适当的体液和细胞免疫反应，以提供持久的广泛保护性免疫。此外，我们认为，环境免疫原的性质和呈递方法都会影响疫苗的免疫特异性和效力，这两个参数都必须优化。因此，提出了以下具体目标：(I)确定不同地理多样性的初级分离株Env蛋白的体液和细胞免疫决定因素，并评估所定义的序列变异对免疫原性和抗原性的影响；(Ii)直接检查已定义的初级包膜变异对先前被证明对同源病毒攻击具有保护作用的实验性EIAV疫苗的保护作用；以及(Iii)开发和评估使用VEE和AAV病毒载体的新型免疫策略，以诱导对不同EIAV挑战的持久广泛保护性疫苗免疫。预计拟议的研究结果将为明确的自然环境变异对免疫表型的影响、挑战环境变异与疫苗效力的关系以及病毒载体疫苗实现保护性免疫的潜力提供新的见解。因此，这些EIAV研究的结果应该是对其他动物慢病毒系统中正在进行的疫苗研究的补充，并与设计和评估候选人类艾滋病疫苗有关。