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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：
9389653
负责人：
LEE Mark WETZLER
金额：
$ 72.82万
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 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9389653
关键词：
Adhesions Animal Model Antibiotic Resistance Antibiotics Antigens Bacterial Adhesins Bacterial Infections Biological CEACAM1 CEACAM5 gene Ceftriaxone Cell model Cervical Data Defect Development Diestrus Disease Ectopic Pregnancy Epithelium Estradiol Estrus Ethics Event Exposure to Female Fibrosis Future Genes Genetic Genitourinary system Goals Gonorrhea Grant Gray unit of radiation dose HIV Human Immune Immune response Immunity Immunological Models Incidence Infection Infertility Inflammation Inflammatory Response Investigation Laboratories Life Modeling Molecular Models Mus Natural Immunity Neisseria gonorrhoeae Neisseria meningitidis Pan Genus Pattern Pelvic Inflammatory Disease Phase Predisposition Public Health Publishing Quinolones Receptor Cell Research Role Sister Solid Specificity Symbiosis Time Transgenic Mice Tube VDAC1 gene Vaccination Vaccine Design Vaccines Vagina Virulence Factors Virus Shedding Work acquired immunity cytokine fitness gonococcal porin human data humanized mouse in vivo insight microbial molecular modeling mouse model neutrophil nonhuman primate pathogen reproductive reproductive tract response success tool transcriptome sequencing transcriptomics transmission process vaccine candidate vaccine development vaccine evaluation

项目摘要

PROJECT SUMMARY 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 gonococcal (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 both transcervical induced upper genital tract (UGT) and intravaginal induced lower genital tract (LGT) infection models utilizing humanized transgenic mice expressing CEACAM 1 or CEACAM5 respectively. The aims of this grant are to 1) Evaluate the ability of high priority gonococcal vaccine candidates (porin, OMV and LOS derived mimotopes) to protect humanized TG mice from LGT or UGT GC infection, 2) Determine which immune defects may allow for enhanced infection in WT mice (to aid in discerning potential correlates of immunity) and 3) Examine pattern of in vivo expressed GC genes by RNAseq transcriptomics and Compare to similar data from humans. If the aims are fulfilled, a new model for gonococcal vaccine evaluation will be established and validated by comparison to human infection, 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.

项目总结