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/艾滋病困扰着 3300 万人，迫切需要一种能够阻止艾滋病毒传播的预防性疫苗。我们将改造先驱的缓解型口腔细菌，以创建一种安全有效的重组疫苗载体来对抗婴儿和成人艾滋病。基于轻链球菌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艾滋病毒的粘膜传播。重组轻链球菌载体将是安全的，并且能够在婴儿和成人的口腔和鼻咽部大量且持久地定植，以引发强大的粘膜免疫。在这项研究中，我们将开发第一个临床前轻链球菌定植的小动物模型，以 评估基于轻链球菌的疫苗策略对于预防艾滋病的潜在用途。重组轻链球菌将被工程化，以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测试，以评估重组轻链球菌是否会诱导口腔、肠道和阴道的粘膜免疫，而口腔、肠道和阴道是主要的粘膜免疫。艾滋病病毒的进入和复制门户。这些研究是开发重组轻链球菌作为针对儿童和成人艾滋病及其他疾病的潜在候选疫苗载体的关键一步。 公共卫生相关性：艾滋病毒/艾滋病是一个重大的全球公共卫生问题，需要立即解决。我们建议开发一种创新的重组轻症链球菌疫苗技术，以对抗艾滋病毒和其他使人衰弱的疾病。