Peptide-VLP Vaccines

肽-VLP疫苗

• 批准号: 10588246
• 负责人: Bryce C Chackerian
• 金额: $ 31.05万
• 依托单位: HENRY M. JACKSON FDN FOR THE ADV MIL/MED
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-26 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10588246
• 关键词: Affect; Antibiotic Resistance; Antibodies; Antibody Response; Antigenic Variation; Antigens; Bacteriophages; Binding; Carrier Proteins; Ceftriaxone; Cervical; Cervicitis; Clinical; Collaborations; Complement; Core Facility; Country; Ectopic Pregnancy; Engineering; Epitopes; Fright; Goals; Gonorrhea; Human; Human Papillomavirus; Immune Evasion; Immune response; Immunologics; Incidence; Infection; Iron; Licensure; Measures; Mediating; Membrane; Membrane Proteins; Modeling; Mucosal Immune Responses; Mucous Membrane; Mus; Neisseria gonorrhoeae; Pathogenesis; Pathway interactions; Pelvic Inflammatory Disease; Peptides; Phase; Play; Reproductive Tract Infections; Research; Resources; Role; Serum; Services; Sexually Transmitted Diseases; Specificity; Surface; Techniques; Technology; Testing; Transferrin; Transferrin-Binding Protein A; United States; Urethritis; VDAC1 gene; Vaccine Production; Vaccines; Variant; Virus-like particle; azithromycin resistance; bactericide; chemical conjugate; chronic pelvic pain; efficacy testing; efflux pump; flexibility; genital infection; gonorrhea vaccine; human pathogen; immunogenic; immunogenicity; mouse model; novel vaccines; prophylactic; recombinant virus; reproductive tract; resistant strain; technology platform; tubal infertility; vaccine candidate; vaccine development; vaccine immunogenicity; vaccine platform; vaccine-induced antibodies

PROJECT SUMMARY Neisseria gonorrhoeae (Ng) is an obligate human pathogen that causes gonorrhea, one of the most common sexually transmitted infections. The incidence of Ng infection in the United States is rising, and the emergence of multi-antibiotic resistant strains have led to fears that treatment options for gonorrhea are decreasing. The overall goal of the Gonorrhea Vaccine Cooperative Research Center (GV CRC) is to identify promising new vaccine candidates for Ng. In this project, our central hypothesis is that an effective gonorrhea vaccine can be developed by engineering highly immunogenic vaccines that specifically target critical surface-exposed Ng epitopes. To do this, we will utilize a flexible and highly immunogenic vaccine platform technology that is based of bacteriophage virus-like particles (VLPs). In Aim 1, we will engineer VLP-based vaccines that target surface- exposed epitopes of four Ng antigens that are potential vaccine targets. In Aim 2, we will measure the immunogenicity of candidate vaccines and assess the bactericidal and opsonophagocytic activity of induced antibodies. In Aim 3, we will test the efficacy of the most promising VLP vaccines in challenge studies using mouse genital tract infection models. These studies will benefit from extensive collaborations with the GV CRC Core facilities and complement the vaccine development efforts of the other Projects.

项目摘要 淋病奈瑟菌（Ng）是一种专性人类病原体，可引起淋病， 性传播感染美国的Ng感染发病率正在上升， 多重抗生素耐药菌株的出现导致人们担心淋病的治疗选择正在减少。的 淋病疫苗合作研究中心（GV CRC）的总体目标是确定有前途的新的 Ng的候选疫苗。在这个项目中，我们的中心假设是，一种有效的淋病疫苗可以 通过工程化高免疫原性疫苗开发，这些疫苗专门针对关键的表面暴露的Ng 表位为了做到这一点，我们将利用一种灵活的和高免疫原性的疫苗平台技术， 噬菌体病毒样颗粒（VLP）。在目标1中，我们将设计基于VLP的疫苗，靶向表面- 四种Ng抗原的暴露表位是潜在的疫苗靶标。在目标2中，我们将测量 候选疫苗的免疫原性，并评估诱导的疫苗的杀菌和调理吞噬活性。 抗体的在目标3中，我们将在攻毒研究中测试最有前途的VLP疫苗的有效性， 小鼠生殖道感染模型。这些研究将受益于与GV CRC的广泛合作 核心设施，并补充其他项目的疫苗开发工作。