Oral immunization against HIV/AIDS with prime-boost strategies

采用初免-加强策略口服艾滋病毒/艾滋病免疫

• 批准号: 7995820
• 负责人: Shiu-Lok Hu
• 金额: $ 53.81万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7995820
• 关键词: AIDS/HIV problem; Adult; Attenuated; Clinical; Development; Drug Formulations; HIV; HIV Infections; Immunity; Immunization; Infant; Ingestion; Ligands; Macaca; Milk; Modeling; Mothers; Oral; Oral mucous membrane structure; Poxviridae; Preventive; Proteins; Regimen; SIV; Safety; Technology; Toll-like receptors; Vaccination; Vaccines; cost effective; immunogenicity; mucosal site; nonhuman primate; protective efficacy; response; simian human immunodeficiency virus; transmission process; vaccination strategy

DESCRIPTION (provided by applicant): Mucosal transmission represents the predominant mode of global HIV acquisition. Oral transmission is rare. However, it does occur, in adults and in infants, with the latter occurring most likely through ingestion of milk from HIV-infected mothers. If an effective vaccine can be formulated for orally delivery, it is likely to protect not only against oral and other mucosal transmission, but also enhance vaccine access through its ease of administration, thus providing a cost-effective preventive approach against HIV/AIDS. Over the past two decades, our lab has demonstrated the feasibility of parenteral immunization with a poxvirus prime/protein boost strategy, resulting in complete or partial protection against mucosal SIV or SHIV challenge in macaques. In this application, we propose to extend these findings and to leverage recent developments in natural Toll-like receptor (TLR) ligands and oral formulation technologies to explore the possibility of adapting this immunization approach for oral vaccination against HIV/AIDS. The overall hypothesis we propose is that effective oral delivery of poxvirus and protein vaccines in a prime-boost immunization strategy will generate greater oral and mucosal responses than parenteral immunizations, resulting in protection against mucosal challenge. The Specific Aims are: (1) To evaluate the safety and immunogenicity of oral delivery of a replication competent, attenuated poxvirus vaccine; (2) To evaluate the safety and immunogenicity of protein vaccines adjuvanted with a natural TLR ligand and formulated for oral delivery; (3) To compare the immunogenicity of poxvirus prime and protein boost approach in different oral and parenteral delivery regimens; (4) To evaluate the protective efficacy of oral delivered prime/boost vaccines against mucosal challenge in non-human primate models. Results from these studies are likely to help elucidate the protective mechanisms against HIV/AIDS and inform the clinical development of the poxvirus prime/protein boost immunization concept. PUBLIC HEALTH RELEVANCE: Most HIV infections result from mucosal transmission, including transmissions through the oral mucosa. Orally delivered vaccines are easy to administer and are likely to induce immunity at mucosal sites. In this proposal, we will examine oral formulations and delivery of a prime-boost vaccination strategy for its potential to generate protective immunity in macaque models.

描述（由申请人提供）：粘膜传播是全球艾滋病毒感染的主要模式。口头传播很少见。然而，这种情况确实发生在成人和婴儿身上，后者最有可能是通过摄入感染艾滋病毒的母亲的牛奶而发生的。如果可以配制一种有效的口服疫苗，它不仅可以防止口腔和其他粘膜传播，而且可以通过其易于给药的方式提高疫苗的可及性，从而提供一种具有成本效益的艾滋病毒/艾滋病预防方法。在过去的二十年里，我们的实验室已经证明了使用痘病毒初免/蛋白加强策略进行肠外免疫的可行性，从而可以完全或部分保护猕猴免受粘膜 SIV 或 SHIV 攻击。在本申请中，我们建议扩展这些发现，并利用天然 Toll 样受体 (TLR) 配体和口服制剂技术的最新进展，探索将这种免疫方法用于口服艾滋病毒/艾滋病疫苗接种的可能性。我们提出的总体假设是，在初免-加强免疫策略中有效口服痘病毒和蛋白质疫苗将比肠胃外免疫产生更大的口腔和粘膜反应，从而防止粘膜攻击。具体目标是： (1) 评估口服具有复制能力的减毒痘病毒疫苗的安全性和免疫原性； (2) 评估以天然TLR配体为佐剂并配制为口服给药的蛋白质疫苗的安全性和免疫原性； (3) 比较不同口服和肠胃外给药方案中痘病毒初免和蛋白加强方法的免疫原性； (4) 评估口服初免/加强疫苗对非人灵长类动物模型中粘膜攻击的保护功效。这些研究的结果可能有助于阐明艾滋病毒/艾滋病的保护机​​制，并为痘病毒初免/蛋白加强免疫概念的临床开发提供信息。 公共卫生相关性：大多数艾滋病毒感染是由粘膜传播引起的，包括通过口腔粘膜传播。口服疫苗易于施用，并且可能在粘膜部位诱导免疫力。在本提案中，我们将研究口服制剂和初免-加强疫苗接种策略的实施，以了解其在猕猴模型中产生保护性免疫力的潜力。