Gamma-2 Herpesviruses as Vaccine Vectors for AIDS

Gamma-2 疱疹病毒作为艾滋病疫苗载体

• 批准号: 7027044
• 负责人: Ronald C Desrosiers
• 金额: $ 49.29万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-15 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7027044
• 关键词: AIDS vaccines; Alphaherpesvirinae; B lymphocyte; Gammaherpesvirinae; Macaca mulatta; attenuated microorganism; biotechnology; flow cytometry; gene expression; immune response; latent virus infection; live vaccine; monocyte; nonhuman therapy evaluation; plasmids; recombinant DNA; recombinant virus; simian immunodeficiency virus; vaccine development; vaccine evaluation; vector vaccine; virus antigen; virus infection mechanism; virus load

DESCRIPTION (provided by applicant): Live attenuated SIV deletion mutants remain the gold standard for vaccine protection against SIV239, SIV251 and other similar AIDS-inducing strains in rhesus monkeys. Viral persistence and persistence of immune responses that are up, on, and active at the time of challenge may be one important factor for why the live attenuated vaccine approach protects so well against SIV challenge. The goal of the proposed studies is to determine whether durable cellular and humoral immune responses induced by a persisting herpesvirus can match, or come close to matching, the live attenuated approach for the potency and durability of protection. A gamma-2 herpesvirus (rhesus monkey rhadinovirus; RRV) will be used to express SIV antigens and to analyze protective capabilities in rhesus monkeys. The biological properties and gene content of the gamma herpesviruses differ from those of the alpha and beta herpesviruses and this in turn may influence the qualitative nature of the immune response and ability to provide protection against SIV/HIV. The persistence of RRV vaccine vectors may also be conveniently monitored in the blood and lymphoid organs. Promoter usage, nature of the expression cassette, site of insertion into the RRV genome, and route of administration will be varied in order to optimize the induction of protective immunity. Our studies address the fundamental utility of recombinant, persisting RRV as a vaccine vehicle. They are not directly directed toward trials in people in the near future. Nonetheless, it is relevant to note that a live attenuated herpesvirus vaccine is currently used in humans for varicella zoster and that human infection by the RRV-related virus of humans (KSHV; HHV-8) is rather infrequent (<3%) in North American and European populations. Thus, it is not unreasonable to envision a recombinant KSHV that is missing several genes and capable of expressing HIV antigens for use as a vaccine in people.

描述（由申请人提供）：SIV缺失突变体是针对SIV239，SIV251和其他类似艾滋病诱导的恒河猴的疫苗保护的金标准。在挑战时，在挑战时，上升和活跃的免疫反应的病毒持久性和持久性可能是为什么活衰减的疫苗方法能够很好地保护SIV挑战的一个重要因素。拟议的研究的目的是确定持续的疱疹病毒引起的持久性细胞和体液免疫反应是否可以匹配或接近匹配，即为保护的效力和耐用性而实现的衰减方法。 γ-2疱疹病毒（恒河猴rr鼠； RRV）将用于表达SIV抗原并分析恒河猴中的保护能力。伽马疱疹病毒的生物学特性和基因含量与α和β疱疹病毒的生物学特性不同，这反过来又可能影响免疫反应的定性性质和提供针对SIV/HIV的保护能力。在血液和淋巴器官中，RRV疫苗载体的持久性也可以方便地监测。为了优化保护性免疫的诱导，将有所不同，启动子使用，表达盒的性质，插入RRV基因组的位点以及给药途径。我们的研究介绍了重组，将RRV持续为疫苗的基本效用。在不久的将来，他们并非直接针对人们的审判。尽管如此，要注意的是，目前在人类中使用了活死的疱疹病毒疫苗，用于水痘带状疱疹，并且北美和欧洲人口中与RRV相关的人类（KSHV； HHV-8）的人类感染（KSHV； HHV-8）相当不佳（<3％）。因此，设想一个重组KSHV并不是没有道理的，该重组KSHV缺少几个基因并能够表达艾滋病毒抗原作为人的疫苗。