Recombinant streptococcus mitis vaccine technology against HIV and other diseases

描述(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。我们将改造首创的微型链球菌口腔细菌，创造一种安全有效的针对婴儿和成人艾滋病的重组疫苗载体。基于S.mitis的疫苗策略将具有先锋细菌的独特特征，这将使该策略有效地对抗艾滋病毒的粘膜传播。重组米氏沙门氏菌载体具有较强的安全性，能够在婴幼儿和成人的口腔和鼻咽部大量、持久地定植，从而诱导出较强的黏膜免疫。在这项研究中，我们将建立第一个临床前米氏葡萄球菌定植的小动物模型，以 评估以S.mitis为基础的疫苗策略在预防艾滋病方面的潜在有用性。重组链球菌将表达不同定位信号的HIV/SIV抗原，随后将进行临床前免疫原性测试，以评估重组链球菌是否会在口腔、肠道和阴道诱导黏膜免疫，而口腔、肠道和阴道是艾滋病病毒进入和复制的主要门户。这些研究是开发重组米氏链球菌作为预防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。

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.