HIV VACCINE RATIONALE

HIV 疫苗的基本原理

• 批准号: 7958598
• 负责人: JULIA L HURWITZ
• 金额: $ 5.81万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958598
• 关键词: Address; Animal Testing; Animals; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Control Animal; Disease; Ensure; Evaluation; Exposure to; Funding; Future; Gold; Grant; HIV vaccine; HIV-1 vaccine; Human; Immune response; Immunologic Deficiency Syndromes; Infection; Institution; Light; Macaca; Methods; Modification; Primates; Research; Research Personnel; Resources; Rest; Source; Testing; Time; United States National Institutes of Health; Vaccines; Vaccinia virus; Viola; Viral Proteins; Virus; Virus Diseases; immunogenic; improved; neutralizing antibody; research study; simian human immunodeficiency virus; superinfection; vaccine development; vaccine safety; vector

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. This year, we examined two issues pertinent to the discovery of a successful HIV-1 vaccine. With experiment 1, we addressed an important debate concerning the ability of an immunodeficiency virus to elicit a protective immune response. With experiment 2 we tested the ability of a multi-vectored (DNA, vaccinia virus, protein), multi-envelope HIV-1 vaccine to protect against a heterologous SHIV challenge. Methods: In experiment 1, two macaques received an inoculation with SHIV KU-1 and were rested for 10 months, after which animals were exposed to SHIV 89.6P. This experiment was conducted prior to 2008, but evaluation was completed this year. In experiment 2, groups of macaques received multi-vectored, multi-envelope vaccines. Some animals received vaccinia virus that had been inactivated by ultra-violet light. Test and control animals were challenged with SHIV 89.6P. Results: In experiment 1, we found that SHIV KU-1 infection elicited diverse neutralizing antibody activities that improved during the e10 month period. After exposure to SHIV 89.6P, all control animals were infected and most succumbed to disease. In contrast, among test animals, one showed no evidence of superinfection and the second showed virus at only one time point. Neither animal showed signs of disease. Experiment 2 showed that the multi-envelope vaccine protected against disease and that the vaccinia virus recombinant vector was immunogenic even after inactivation. Discussion: Experiment 1 clearly demonstrated that infected animals could mount a protective immune response against superinfection. We suggest that 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. Experiment 2 demonstrated the potency of a multi-envelope vaccine, while validating a vector modification that might be used in future clinical trials to ensure HIV-1 vaccine safety.

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。 今年，我们研究了与发现成功的HIV-1疫苗有关的两个问题。通过实验1，我们解决了有关免疫缺陷病毒引起保护性免疫反应能力的重要辩论。通过实验2，我们测试了多矢量（DNA，vercinia病毒，蛋白质），多Envelope HIV-1疫苗防止异源SHIV挑战的能力。方法：在实验1中，两个猕猴接种了SHIV KU-1，并休息了10个月，然后将动物暴露于SHIV 89.6便士。该实验是在2008年之前进行的，但今年进行了评估。在实验2中，一组猕猴接收了多载体的多层疫苗。一些动物接受了超紫罗莱氏光的疫苗病毒。 SHIV 89.6便士对测试和对照动物进行了挑战。结果：在实验1中，我们发现SHIV KU-1感染引起了E10个月期间改善的各种中和抗体活性。暴露于SHIV 89.6便士后，所有对照动物都被感染，最大程度地屈服于疾病。相比之下，在测试动物中，没有显示超染色的迹象，第二个仅显示一个时间点病毒。两种动物都没有表现出疾病的迹象。实验2表明，多个电动疫苗免受疾病的侵害，即使在失活后，离甲状腺病毒重组载体也是免疫原性的。讨论：实验1清楚地表明，受感染的动物可以对近代感染产生保护性免疫反应。我们建议这种保护状态可以作为HIV-1疫苗开发的“金标准”，因为人们对人类的免疫缺陷病毒感染有类似的保护程度。实验2证明了多个玻璃疫苗的效力，同时验证了可能在以后的临床试验中使用以确保HIV-1疫苗安全性的载体修饰。