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）：粘膜传播代表全球HIV获取的主要模式。口服传播很少见。但是，它确实发生在成年人和婴儿中，后者最有可能通过摄入艾滋病毒感染的母亲摄入牛奶而发生。如果可以制定有效的疫苗以口服输送，则可能不仅可以防止口服和其他粘膜传播，而且还可以通过易于给药来增强疫苗接种，从而为艾滋病毒/艾滋病提供了具有成本效益的预防方法。在过去的二十年中，我们的实验室通过Poxvirus Prime/蛋白质增强策略证明了肠胃外免疫的可行性，从而在猕猴中对粘膜SIV或SHIV挑战进行了完全或部分保护。在此应用中，我们建议扩展这些发现，并利用自然收费受体（TLR）配体和口服配方技术的最新发展，以探索适应这种免疫接种方法以抗HIV/AIDS的免疫方法。我们提出的总体假设是，在促进型免疫策略中有效口服痘病毒和蛋白质疫苗将产生比肠胃外免疫更大的口服和粘膜反应，从而防止粘膜挑战。具体目的是：（1）评估复制能力，减弱的痘病毒疫苗的口服递送的安全性和免疫原性； （2）评估与天然TLR配体辅助并配制以口服递送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递送方案中痘病毒素和蛋白质增强方法的免疫原性； （4）评估在非人类灵长类动物模型中，针对粘膜挑战的口服提供的原始/增强疫苗的保护性疗效。这些研究的结果很可能有助于阐明针对HIV/AIDS的保护机制，并为Poxvirus Prime/Protein Brime/蛋白质增强免疫概念的临床发展提供了信息。 公共卫生相关性：大多数HIV感染是由粘膜传播引起的，包括通过口腔粘膜传播。口服输送的疫苗易于施用，并且很可能在粘膜部位诱导免疫力。在此提案中，我们将检查口服配方和提供促进疫苗接种策略，以便在猕猴模型中产生保护性免疫。