Recombinant streptococcus mitis vaccine technology against HIV and other diseases

针对艾滋病毒和其他疾病的重组轻链球菌疫苗技术

• 批准号: 8329259
• 负责人: Mark Cayabyab
• 金额: $ 14.93万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8329259
• 关键词: AIDS Vaccines; AIDS prevention; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Address; Adult; Animal Model; Animals; Antibody Formation; Antigens; Bacteria; CD8B1 gene; Cavia; Cell Wall; Cellular Immunity; Childhood; Clinical Trials; Commit; Cytoplasm; Data; Development; Disease; Engineering; Erythromycin; Funding; Gagging; Genes; Genetic; Genome; HIV; HIV Antigens; HIV vaccine; HIV-1; Human; Human Milk; Immunologics; Immunosuppression; Infant; Infection; Intervention; Location; Microbe; Modeling; Monkeys; Mucosal Immune Responses; Mucosal Immunity; Mus; Nasopharynx; Neonatal; North Carolina; Oral; Oral cavity; Oral mucous membrane structure; Organism; Population; Preclinical Testing; Prevention strategy; Preventive; Public Health; Rattus; Recombinant Vaccines; Recombinants; Research Priority; Resistance; SIV; Safety; Signal Transduction; Solutions; Streptococcus mitis; Surface; System; T cell response; T-Lymphocyte; Technology; Testing; Universities; Vaccination; Vaccine Antigen; Vaccines; Vagina; Virus; bacterial vector; base; design; immunogenicity; innovation; neutralizing antibody; nonhuman primate; novel; oral bacteria; oral vaccine; pre-clinical; preclinical evaluation; preclinical safety; programs; prototype; transmission process; vaccination strategy; vaccine candidate; vaccine delivery; vector; vector vaccine; vector-based vaccine

DESCRIPTION (provided by applicant): HIV/AIDS afflicts 33 million people and a preventive vaccine that will stop transmission of HIV is desperately needed. We will engineer the pioneer Streptococcus mitis oral bacterium to create a safe and effective recombinant vaccine vector against infant and adult AIDS. The S. mitis-based vaccine strategy will have the unique features of the pioneer bacterium that will make this strategy effective against mucosal transmission of HIV. The recombinant S. mitis vector will be safe and capable of colonizing the oral cavity and nasopharynx of infants and adults abundantly and persistently to elicit robust mucosal immunity. In this study, we will develop the first preclinical small animal model of S. mitis colonization to evaluate the potential usefulness of the S. mitis-based vaccine strategy for the prevention of AIDS. The recombinant S. mitis will be engineered to express HIV/SIV antigens with different localization signals and subsequent preclinical immunogenicity testing will be conducted to assess whether recombinant S. mitis will induce mucosal immunity in the oral cavity, gut and vagina, which are the primary portals of entry and replication for the AIDS virus. These studies are a critical step towards developing recombinant S. mitis as a potential candidate vaccine vector against pediatric and adult AIDS and other diseases. PUBLIC HEALTH RELEVANCE: HIV/AIDS is a major global public health problem that needs an immediate solution. We propose to develop an innovative and novel recombinant Streptococcus mitis vaccine technology against HIV and other debilitating diseases.

描述（由申请人提供）：艾滋病毒/艾滋病折磨着3300万人，迫切需要一种预防性疫苗来阻止艾滋病毒的传播。我们将对缓症链球菌口腔细菌的先驱进行工程改造，以创造一种安全有效的重组疫苗载体来对抗婴儿和成人艾滋病。色葡萄基于螨的疫苗策略将具有先锋细菌的独特特征，这将使该策略有效对抗HIV的粘膜传播。重组S. Mitis载体将是安全的，并且能够大量和持久地定殖于婴儿和成人的口腔和鼻咽，以引发强有力的粘膜免疫。在本研究中，我们将建立第一个临床前的小动物模型的S。温和殖民化， 评估S.以螨为基础的预防艾滋病疫苗策略。重组S.将对缓和病毒进行工程改造，使其表达具有不同定位信号的HIV/SIV抗原，随后将进行临床前免疫原性试验，以评估重组S.缓和症将诱导口腔、肠道和阴道中的粘膜免疫，这些是AIDS病毒进入和复制的主要门户。这些研究是开发重组S.作为一种潜在的候选疫苗载体，针对儿童和成人艾滋病和其他疾病。 公共卫生相关性：艾滋病毒/艾滋病是一个需要立即解决的重大全球公共卫生问题。我们建议开发一种创新的和新型的重组链球菌缓症疫苗技术，以对抗艾滋病毒和其他衰弱性疾病。