OMV vaccine against Gonorrhea

淋病 OMV 疫苗

• 批准号: 10478441
• 负责人: Yingru Liu
• 金额: $ 30万
• 依托单位: THERAPYX, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-22 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10478441
• 关键词: Adjuvant; Antibodies; Antigens; Biodegradable microsphere; CD8-Positive T-Lymphocytes; Centers for Disease Control and Prevention (U.S.); Cervical; Communicable Diseases; Complement; Cytolysis; Development; Drug Kinetics; Drug-resistant Neisseria Gonorrhoeae; Encapsulated; Frequencies; Future; Generations; Genital; Genitalia; Goals; Gonorrhea; Human; Immune response; Immune system; Immunity; Immunization; Immunoglobulin G; In Vitro; Incidence; Infection; Interleukin-10; Knock-out; Measures; Mediating; Membrane; Mucous Membrane; Multi-Drug Resistance; Mus; Neisseria gonorrhoeae; Phagocytes; Phase; Phase I Clinical Trials; Play; Preparation; Production; Public Health; Publishing; Reporting; Resistance; Role; Saliva; Serum; Small Business Innovation Research Grant; T-Lymphocyte; Testing; Time; Toxic effect; Vaccine Antigen; Vaccines; Vagina; Vesicle; Woman; Work; adaptive immune response; base; cross immunity; cross reactivity; cytokine; design; draining lymph node; emerging antibiotic resistance; immunoregulation; memory recall; mouse model; mutant; neutralizing antibody; novel; novel strategies; novel vaccines; particle; phase 2 study; public health relevance; reproductive tract; resistant strain; response; scale up; time interval; vaccination strategy; vaccine development; vaccine strategy

ABSTRACT Gonorrhea is a genital tract infection caused by Neisseria gonorrhoeae, which can be acquired repeatedly and does not naturally induce a state of specific protective immunity against reinfection. Despite public health measures, gonorrhea persists at an unacceptably high frequency, and there is no vaccine against it. The continuing emergence of antibiotic resistance threatens to render gonorrhea untreatable. Our findings have revealed that N. gonorrhoeae subverts the immune system for its own benefit by inducing high levels of the immuno-regulatory cytokine, interleukin-10 (IL-10). Using the established murine model of vaginal gonococcal infection, we propose to investigate a novel strategy of vaccination against N. gonorrhoeae, exploiting neutralizing antibody against IL-10 encapsulated in biodegradable micro-particles (GneXa10®) as adjuvant. As vaccine antigen, outer membrane vesicles (OMV) derived from a double- mutant (dm) strain of N. gonorrhoeae, designed to reduce adverse responses to administration in humans, will be used. We will determine the role of serum and mucosal antibody and T-cell cytokine responses to intra-nasal (i.n.) immunization with dmOMV plus GneXa10®, in resistance to challenge infection with both homologous and heterologous strains. Persistence of immunity and recall of memory responses at increasing time intervals after immunization will be evaluated. Functional antibodies active against N. gonorrhoeae will be assessed in vitro. This work will provide proof-of-principle for a vaccine based on gonococcal dmOMVs and GneXa10®. Future SBIR phase II studies will further elucidate mechanisms of cross-protection against diverse strains of N. gonorrhoeae, and validate the expected applicability of scaled-up vaccine development, evaluating yield, bioactivity, batch-to-batch consistency, and shelf stability. This proposal is part of our company’s response to the CDC’s and WHO’s calls for development of novel vaccine approaches in the face of the public health threat posed by antibiotic-resistant N. gonorrhoeae.

抽象的 淋病是由淋病奈瑟菌引起的生殖道感染，可反复感染 尽管在公共场合，但不会自然地诱导针对再次感染的特定保护性免疫力状态。 采取卫生措施后，淋病的发病率持续高得令人无法接受，而且没有针对该病的疫苗 抗生素耐药性的持续出现可能使我们的淋病无法治愈。 研究结果表明，淋病奈瑟菌为了自身利益而破坏免疫系统，通过诱导 使用已建立的小鼠模型获得高水平的免疫调节细胞因子白细胞介素 10 (IL-10)。 为了预防阴道淋球菌感染，我们建议研究一种新的疫苗接种策略。 淋病，利用封装在可生物降解微粒中的针对 IL-10 的中和抗体 (GneXa10®) 作为疫苗抗原，源自双-外膜囊泡 (OMV)。 淋病奈瑟菌突变株（dm），旨在减少人类给药的不良反应， 我们将确定血清和粘膜抗体以及 T 细胞细胞因子反应的作用。 使用 dmOMV 加 GneXa10® 进行鼻内 (i.n.) 免疫，以抵抗两者的攻击感染 同源和异源菌株的免疫持久性和记忆反应的回忆。 免疫后增加时间间隔将评估针对 N.的功能性抗体。 这项工作将为基于淋病的疫苗提供原理验证。 淋球菌 dmOMV 和 GneXa10® 未来的 SBIR II 期研究将进一步阐明其机制。 针对不同淋病奈瑟菌菌株的交叉保护，并验证预期的适用性 扩大疫苗开发规模，评估产量、生物活性、批次间一致性和货架期 该提案是我们公司响应 CDC 和 WHO 发展呼吁的一部分。 面对抗生素耐药性奈瑟氏菌对公众健康造成的威胁，我们需要开发新的疫苗方法。 淋病。