VLP VACCINES FOR HIV PREVENTION

用于预防 HIV 的 VLP 疫苗

• 批准号: 8357486
• 负责人: RICHARD W COMPANS
• 金额: $ 7.43万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357486
• 关键词: AIDS prevention; Adjuvant; Antibody Formation; Antigen Presentation; Antigen-Presenting Cells; Antigens; Dose; Flagellin; Funding; Grant; HIV; HIV Envelope Protein gp120; HIV vaccine; HIV-1; Human; Immunity; Immunoglobulin Variable Region; Infection; Macaca; Membrane; National Center for Research Resources; Particulate; Primates; Principal Investigator; Process; Research; Research Infrastructure; Resources; Source; Structure; Testing; United States National Institutes of Health; Vaccine Antigen; Vaccines; Virion; Virus-like particle; cost; design; env Gene Products; neutralizing antibody; novel; novel strategies; novel vaccines; prophylactic; response; simian human immunodeficiency virus

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. A prophylactic HIV-1 vaccine should elicit broadly cross-reactive neutralizing activity. The gp120-gp41 Env protein on the native virion is the primary target for eliciting neutralizing antibodies. Although several features of Env make it difficult to elicit broadly neutralizing antibodies, progress has been achieved in recent years in enhancing the immunity of Env by modifying its structure, employing novel delivery platforms, and co-administration of adjuvants. The use of virus-like particles (VLPs) has shown great potential as a new vaccine platform. Recent studies have also demonstrated that lower titers of neutralizing antibody can protect against low-dose repeated mucosal SHIV challenge in macaques, which mimics infection of humans by sexual contact. Recently we developed novel approaches to produce Env-enriched chimeric HIV VLPs (cVLPs) and found that such cVLPs containing a membrane-anchored form of flagellin or a variable-region truncated flagellin as adjuvants induced high levels of systemic and mucosal HIV specific antibody responses, with broadened neutralizing activity. Our research is testing the hypothesis that the presence of antigen and adjuvant in the same particulate structure will generate an effective HIV vaccine antigen, by delivering both components simultaneously to the same antigen-presenting cells. The combination of Env antigen presentation in its native state combined with a membrane-anchored adjuvant and mucosal delivery provides a promising approach to stimulate strong nAb response against HIV, designed to block the initial step in the infection process.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 预防性 HIV-1 疫苗应引起广泛的交叉反应中和活性。天然病毒体上的 gp120-gp41 Env 蛋白是引发中和抗体的主要靶标。尽管 Env 的几个特征使其难以引发广泛的中和抗体，但近年来通过修改其结构、采用新型递送平台和佐剂联合施用在增强 Env 的免疫力方面取得了进展。 病毒样颗粒（VLP）的使用已显示出作为新疫苗平台的巨大潜力。最近的研究还表明，较低滴度的中和抗体可以保护猕猴免受低剂量重复粘膜 SHIV 攻击，这种攻击模仿了人类通过性接触感染的情况。 最近，我们开发了生产富含 Env 的嵌合 HIV VLP（cVLP）的新方法，并发现此类 cVLP 含有膜锚定形式的鞭毛蛋白或可变区截短的鞭毛蛋白作为佐剂，可诱导高水平的全身和粘膜 HIV 特异性抗体反应。具有扩大的中和活性。我们的研究正在测试这样的假设：通过将两种成分同时递送至相同的抗原呈递细胞，同一颗粒结构中的抗原和佐剂的存在将产生有效的 HIV 疫苗抗原。 天然状态下的 Env 抗原呈递与膜锚定佐剂和粘膜递送相结合，提供了一种刺激针对 HIV 的强 nAb 反应的有前景的方法，旨在阻断感染过程的初始步骤。