HIV VACCINE RATIONALE

HIV 疫苗的基本原理

• 批准号: 8172940
• 负责人: JULIA L HURWITZ
• 金额: $ 8.41万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172940
• 关键词: Address; Animals; CD4 Positive T Lymphocytes; Computer Retrieval of Information on Scientific Projects Database; Control Animal; Disease; Funding; Gold; Grant; HIV-1; HIV-1 vaccine; Human; Immune response; Immunologic Deficiency Syndromes; Immunologic Surveillance; Individual; Infection; Institution; Macaca; Measurement; Monitor; Monkeys; Relative (related person); Research; Research Personnel; Resources; Rest; Source; Testing; Time; United States National Institutes of Health; Vaccination; Vaccine Design; Vaccines; Viral Load result; Virus; Virus Diseases; design; env Gene Products; neutralizing antibody; prevent; research study; response; simian human immunodeficiency virus; superinfection; vaccine development

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A current debate in the HIV-1 vaccine field concerns the ability of an immunodeficiency virus to elicit a protective response. One argument is that HIV-1 superinfections are frequent in healthy individuals, because virus evades conventional immune surveillance, a serious obstacle to vaccine design. The opposing argument is that protection from superinfection is significant, reflecting a robust immune response that might be harnessed by vaccination to prevent disease. In an experiment designed to address the debate, two macaques received an I.V. inoculation with SHIV KU-1-d (a derivative of SHIV KU-1) and were rested for 10 months. Infection elicited diverse neutralizing antibody activities in both animals. Animals were then exposed to SHIV 89.6P (I.V.), a virus carrying a heterologous envelope protein relative to the vaccine strain. Infection was monitored by viral load and CD4+ T-cell measurements. All control animals were infected and most succumbed to disease. In contrast, protection from superinfection was statistically significant in test monkeys; one animal showed no evidence of superinfection at any time point and the second showed evidence of virus at only one time point over a 6-month observation period. Neither animal showed signs of disease. Perhaps this protective state may serve as a 'gold-standard' for HIV-1 vaccine development, as a similar degree of protection against immunodeficiency virus infections in humans would be much desired.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 HIV-1疫苗现场的当前辩论涉及免疫缺陷病毒引起保护性反应的能力。一个论点是，在健康个体中，HIV-1超级感染是经常出现的，因为病毒逃避了常规的免疫监测，这是疫苗设计的严重障碍。相反的论点是，免受超级感染的保护意义重大，反映出可能通过疫苗接种以预防疾病来避免的强大免疫反应。在旨在解决辩论的实验中，两个猕猴收到了一个i.v.用Shiv Ku-1-D接种（SHIV KU-1的衍生物），并休息10个月。感染引起了两种动物的多种中和抗体活性。然后将动物暴露于Shiv 89.6p（i.v.），这是一种携带异源包膜蛋白相对于疫苗菌株的病毒。通过病毒载荷和CD4+ T细胞测量来监测感染。所有对照动物都被感染，最大程度地屈服于疾病。相比之下，在测试猴子中免受近距离感染的保护具有统计学意义。一只动物在任何时间点都没有表现出超级感染的证据，第二个动物在一个6个月的观察期间仅显示了一个时间点病毒的证据。两种动物都没有表现出疾病的迹象。也许这种保护状态可能是HIV-1疫苗开发的“金标准”，因为对人类的免疫缺陷病毒感染具有类似程度的保护。