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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 预防性HIV-1疫苗应引起广泛的交叉反应性中和活性。天然病毒体上的GP120-GP41 ENV蛋白是引起中和抗体的主要靶标。尽管ENV的几个特征使得很难引起广泛中和抗体，但近年来，通过修改其结构，采用新颖的输送平台以及对佐剂的共同管理来增强ENV的免疫力。 使用病毒样颗粒（VLP）作为新的疫苗平台表现出巨大的潜力。最近的研究还表明，中和抗体的较低滴度可以预防猕猴中的低剂量重复粘膜湿液刺激挑战，这是通过性接触模仿人类感染的。 最近，我们开发了新的方法来生产富含Env的嵌合HIV VLP（CVLP），并发现这种CVLP含有膜锚定形式的鞭毛蛋白或可变区域截短的鞭毛蛋白作为辅助诱导的高水平的全身性和粘膜HIV特异性抗体反应，具有广泛的中性中性化活性。我们的研究是检验了以下假设：相同颗粒结构中抗原和佐剂的存在将通过同时将两个成分交付到相同的抗原呈递细胞中，从而产生有效的HIV疫苗抗原。 ENV抗原在其天然状态中的结合与膜锚定的佐剂和粘膜递送相结合，提供了一种有希望的方法，可以刺激针对HIV的强烈NAB反应，旨在阻止感染过程中的初始步骤。