Gonococcal Vaccine Evaluation in a Humanized Mouse Model

人源化小鼠模型中的淋球菌疫苗评估

基本信息

批准号：
8868920
负责人：
LEE Mark WETZLER
金额：
$ 58.3万
依托单位：
BOSTON MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-17 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8868920
关键词：
Accounting Animal Model Antibiotic Resistance Antibiotics Antigens Bacteria Bacterial Adhesins Bacterial Infections Biological Ceftriaxone Cell model Cervical Complement Factor H Development Diagnostic Disease Dose Ectopic Pregnancy Estradiol Estrus Event Exposure to Female Fibrosis Foundations Future Gene Expression Genes Genetic Genitourinary system Goals Gonorrhea Grant Gray unit of radiation dose HIV Health Human Immune Immune response Immunity Immunization Immunological Models Immunologics Incidence Infection Infertility Investigation Laboratories Lactoferrin Letters Life Membrane Modeling Molecular Models Mucous Membrane Mus Mutant Strains Mice Neisseria gonorrhoeae Neisseria gonorrhoeae protein I Neisseria meningitidis Opsonin Organism Pan Genus Pelvic Inflammatory Disease Phagocytosis Predisposition Public Health Publishing Quinolones Receptor Cell Relative (related person)Research Research Personnel Sister Solid Specificity Transferrin Transgenes Transgenic Mice Transgenic Organisms Universities Vaccine Design Vaccines Vagina Vesicle Virulence Factors Virus Shedding adaptive immunity complement 4b-binding protein fitness gonococcal porin insight killings microbial molecular modeling mouse model neutrophil nonhuman primate pathogen response success tool transmission process vaccine candidate vaccine development vaccine efficacy vaccine evaluation

项目摘要

DESCRIPTION (provided by applicant): Efforts to develop a gonococcal vaccine have continued for over three decades without notable progress. While the significant sequelae of infection in females and solid evidence that concurrent GC infection can enhance HIV transmission have spurred these investigations, this goal has become more urgent given the recent increase in GC antibiotic resistance, especially to ceftriaxone. Two major issues associated with this absence of success have been 1) the lack of an animal model that appreciates the human specificity of gonococcal adhesins and other virulence factors, and 2) the lack of correlates of immunity that can inform vaccine design. The overall objective of this proposal is to evaluate potential gonococcal vaccine candidates in a recently developed GC vaginal infection model utilizing humanized transgenic mice termed NeMo-8. The aims of this grant are to 1) Evaluate the immune response to vaginal gonococcal infection of the humanized TG mice, 2) Determine if infection with live organisms or immunization with killed organisms affords any protection in this mouse model, and 3) Evaluate the efficacy of gonococcal vaccine candidates, including gonococcal porin, gonococcal outer membrane vesicles, and other outer membrane components defined by Novartis Vaccines (see letter). If the aims are fulfilled, a new model for gonococcal vaccine evaluation will be established, correlates of gonococcal immunity will be discerned, and the relative utility of gonococcal vaccine candidates will be determined in order to prioritize and guide their future development towards their ultimate use in humans.

描述（由申请人提供）：开发淋球菌疫苗的努力持续了三十年，没有明显的进展。尽管女性感染的显着后遗症和同时GC感染可以增强HIV传播的可靠证据刺激了这些研究，但考虑到GC抗生素耐药性的最近增加，尤其是头孢曲松酮，这一目标变得更加紧迫。与缺乏成功相关的两个主要问题是1）缺乏一种动物模型，该模型欣赏了淋球菌粘附素和其他毒力因素的人类特异性，以及2）缺乏可以告知疫苗设计的免疫相关性。该提案的总体目的是在最近开发的GC阴道感染模型中评估潜在的淋球菌疫苗候选物，该模型利用人性化的转基因小鼠称为NEMO-8。 The aims of this grant are to 1) Evaluate the immune response to vaginal gonococcal infection of the humanized TG mice, 2) Determine if infection with live organisms or immunization with killed organisms affords any protection in this mouse model, and 3) Evaluate the efficacy of gonococcal vaccine candidates, including gonococcal porin, gonococcal outer membrane vesicles, and other outer membrane由诺华疫苗定义的组件（请参阅字母）。如果实现目标，将建立一个新的淋球菌疫苗评估模型，将辨别淋球菌免疫的相关性，并确定淋球菌疫苗的相对实用性，以确定候选者的相对效用，以确定并指导其未来在人类中的最终发展。