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Pre-clinical evaluation of an adenoviral-based MERS-CoV vaccine

基于腺病毒的 MERS-CoV 疫苗的临床前评估

基本信息

批准号：
8839373
负责人：
ANDREA GAMBOTTO
金额：
$ 17.86万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-10 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8839373
关键词：
Adenovirus Vector Adenoviruses Animal Model Animals Antigens B-Lymphocytes Binding Blood group antigen S Camels Cessation of life Characteristics Chickens Clinical Coronavirus Coronavirus Infections Development Dipeptidyl Peptidases Disease Dose Dromedaries Effectiveness Equilibrium Family suidae France Germany Goals Growth Human Immune response Immunity Immunization Immunization Schedule Immunohistochemistry In Situ Hybridization Inbred BALB C Mice Infection Influenza International Intranasal Administration Italy Lead Length Link Lung diseases Measures Mediating Middle East Middle East Respiratory Syndrome Coronavirus Modeling Monitor Monkeys Mus Names Nose Organ Oryctolagus cuniculus Population Preclinical Testing Protein S Receptor Cell Recombinant Vaccines Recombinants Regimen Respiratory Syncytial Virus Vaccines Route Safety Severe Acute Respiratory Syndrome Sheep Source Spain Survival Analysis Swab Symptoms Syndrome T cell response T-Lymphocyte Taxonomy Testing Titrations Vaccinated Vaccines Viral Virulence Virus Virus Shedding base efficacy testing immunogenicity in vivo influenza virus vaccine meetings mortality mouse model neutralizing antibody novel particle pre-clinical public health relevance rectal research clinical testing respiratory response subcutaneous therapeutic development vaccine candidate vaccine development

项目摘要

DESCRIPTION (provided by applicant): Middle East Respiratory Syndrome coronavirus (MERS-CoV) has recently emerged as causative agent of severe respiratory disease in humans. Two hundred and six cases of MERS-CoV infection have been confirmed to date, including 71 deaths. Most infections were geographically linked to the Middle East, but cases also occurred in the UK, Germany, France, Italy and Spain. Dromedary camels are likely the reservoir for MERS-CoV virus. The MERS-CoV spike (S) protein, a characteristic structural component of the viral envelope, is considered a key target of vaccines against coronavirus infection, as we and other have previously demonstrated for severe acute respiratory syndrome (SARS) infection. As an initial attempt to develop a MERS-CoV vaccine, we constructed two recombinant adenoviral vectors encoding the full-length MERS-CoV spike (S) protein (Ad5.MERS-S) and the S1 domain of S protein (Ad5.MERS-S1), which mediates binding to the dipeptidyl peptidase 4, which serves as the host cell receptor of MERS-CoV. The safety profile and the growth characteristics of adenoviral-based vaccines make them suitable MERS-CoV vaccine candidates for preclinical testing. Over the past 15 years, we have demonstrated the extraordinary efficacy of adenoviral vaccine platform in eliciting T and B cell-specific responses to the desired antigens and have been involved in developing promising SARS, influenza and RSV vaccines. Here, we hypothesize that subcutaneous (SQ) and/or intranasal administration (IN) of Ad5.MERS vaccines will elicit MERS-CoV-specific immunity, which will lead to the protection of immunized animals. Ultimately our goal is to develop a veterinary vaccine to target dromedary camels. We will test our hypothesis with four specific aims which will: a) test the immunogenicity of the Ad5.MERS vaccine in a mouse model; b) define the optimal immunization schedule and route of administration; c) establish a MERS-CoV challenge model and d) determine the ability of the selected Ad5.MERS vaccine to protect animal from MERS-CoV challenge in the absence of enhanced disease.