An Expanded Multivalent Vaccine to Prevent MDR Shigella and ETEC Disease

预防 MDR 志贺氏菌和 ETEC 疾病的扩展多价疫苗

• 批准号: 10364710
• 负责人: Eileen M. Barry
• 金额: $ 63.82万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-15 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10364710
• 关键词: 5 year old; Adhesions; Adult; Animals; Antigens; Antimicrobial Resistance; Attenuated; Biological Models; Centers for Disease Control and Prevention (U.S.); Child; Clinical Data; Clinical Trials; Combined Vaccines; Data; Developing Countries; Disease; Disease Outbreaks; Engineering; Enterotoxins; Epidemiology; Evaluation; Funding; Future; Genes; Goals; Heterophile Antigens; Human; Immune response; Immunity; Immunization; Infection; Licensure; Maintenance; Mass Immunization; Methods; Minor; Modeling; Mucous Membrane; Multi-Drug Resistance; Mutation; Oral; Pathogenesis; Plasmids; Population; Production; Public Health; Research Personnel; Route; Safety; Scientist; Serotyping; Shigella; Shigella Vaccines; Shigella flexneri; Shigella sonnei; Surface; Therapeutic Intervention; Toxin; Toxoids; Translating; Vaccination; Vaccine Design; Vaccines; Virulence; Virulence Factors; Visit; colonization factor antigens; efficacy evaluation; enteric pathogen; enterotoxigenic Escherichia coli; epidemiologic data; experience; guinea pig model; high risk population; immunogenicity; improved; mouse model; neutralizing antibody; new technology; novel; oral vaccine; passive antibodies; pathogen; pathogenic bacteria; pre-clinical; preclinical evaluation; prevent; programs; protective efficacy; research clinical testing; resistance mechanism; resistant Shigella; response; vaccine candidate; vaccine development; vaccine formulation; vector; volunteer

The goal of this proposal is to construct a vaccine that is broadly protective against the epidemiologically most important Shigella serotypes and toxin and colonization factor types of enterotoxigenic E. coli (ETEC), two enteropathogens of substantial public health importance to the U.S. and global populations. Both pathogens are designated serious threats by the Centers for Disease Control (CDC) in the U.S. due to increasing multidrug resistance leading to fewer options for therapeutic intervention. Shigella and ETEC readily acquire antimicrobial resistance mechanisms and additional virulence factors, making these pathogens important emerging threats. An oral vaccine with broad coverage against the most prevalent circulating isolates would be beneficial to multiple populations, including: 1) adult and child travelers who visit less developed countries where these infections are hyperendemic; 2) children and adults in certain high risk populations in the US; 3) children < age 5 years in developing countries, and 4) for mass immunization to control natural or deliberate outbreaks. The vaccine will consist of a mixed inoculum of 6 live attenuated strains of Shigella expressing ETEC colonization factor antigens and antigens to induce toxin neutralizing antibodies against heat labile (LT) and heat stable (ST) toxins. Oral immunization is an effective method for inducing mucosal as well as systemic immune responses believed to be important in protection against these enteropathogens and oral delivery is a practical route for product deployment and for enhancing compliance. We are taking advantage of the successful completion of five attenuated Shigella vaccine strains expressing heterologous antigens during the previous CETR funding period, and using current epidemiological data, as well as novel technological advances, to improve and broaden the vaccine formulation in order to maximize the protective efficacy of this Shigella-ETEC vaccine product and optimize features for production. Our specific objective is to complete vaccine candidate optimization and pre- clinical evaluation to enable IND submission for advancement to clinical trials. This project relates directly to the overarching goal of this Program to develop active vaccination and passive antibody strategies to prevent disease caused by multidrug-resistant bacterial pathogens. The collective expertise provided by CETR project investigators and collaborating scientists along with the Center for Vaccine Development's experience in translating products through manufacture and clinical evaluation, will accelerate efforts to advance vaccine development.

这项提议的目标是构建一种疫苗，可以广泛地预防流行病学上最严重的疾病