Mucosal Vaccines for Brucellosis

布鲁氏菌病粘膜疫苗

基本信息

批准号：
9079710
负责人：
David W Pascual
金额：
$ 37.5万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-01-20 至 2020-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9079710
关键词：
Adopted Aerosols Affect Affinity Animal Model Animals Antibiotic Therapy Antibiotics Arthritis Attenuated Live Virus Vaccine Attenuated Vaccines Benign Brucella Brucella Vaccine Brucella abortus Brucella melitensis Brucellosis Cellular Immunity Cholera Chronic Clinical Communicable Diseases DNA Dairy Products Development Disease Elements Endocarditis Experimental Animal Model Future Goals Goat Headache Human Immune response Immunity Immunization Incidence Induced Abortion Infection Ingestion Interferon Type II Interleukin-12 Intestines Joints LacZ Genes Learning Licensing Life Link Liver Livestock Lung M cell Malaise Meat Milk Mucous Membrane Mus Neurologic Nose Oral Oropharyngeal Outcome Population Production Regimen Research Route Safety Shigella Infections Site Socioeconomic Status Spleen Study models Subunit Vaccines Symptoms Systemic disease T-Lymphocyte TNF gene Testing Tissues Tuberculosis Tularemia Typhoid Fever Vaccination Vaccines Work attenuation economic impact efficacy testing flu global health human disease human morbidity immunogenicity improved mucosal vaccination mucosal vaccine mutant neglect nitric oxide reductase novel pathogen prototype public health relevance research clinical testing response unpasteurized vaccination strategy vaccine development vaccine efficacy vaccine evaluation

项目摘要

DESCRIPTION (provided by applicant): The highly infectious Gram-negative Brucella remains a global health threat and is responsible for the disease, brucellosis. In humans, B. melitensis is believed to be responsible for most infections, and it is naturally transmitted via ingestion of unpasteurized dairy products or aerosols of infected animal products resulting in infection of naso-oropharyngeal tissues. Although infection primarily occurs following a mucosal exposure, it can cause a systemic disease manifested by its flu-like symptoms. Despite aggressive antibiotic treatment, it can still result in a recurring sequelae evident as undulant fever and arthritis. Brucellae survival within the host is linked to its ability to evade intracellular recognition, thu, allowing them to sequester in various tissues. Vaccines that can recapitulate aspects of Brucella infection should prove effective in protecting against infection. Hence, we hypothesize that a vaccine that mimics aspects of natural mucosal B. melitensis infections and capable of stimulating cell-mediated immunity via the production of TNF-a and IFN-g will be protective against mucosal and systemic Brucella challenges. To enable this approach, we have recently developed a vaccine prototype that can confers complete protection in most cases with no detectable brucellae in spleens or lungs. Given the potency of this vaccine, we propose to test our hypothesis using two animal models to determine the efficacy of this vaccine against wild-type B. melitensis challenges. Studies in Specific Aim 1 will establish a mucosal (oral, nasal, or oral + nasal) immunization strategy for conferring protection to B. melitensis and to heterologous Brucella species. Studies in Specific Aim 2 will establish similar mucosal immunization strategy in goats, a natural host for B. melitensis, for conferring protection against B. melitensis-induced abortion. Studies in Specific Aim 3 will evaluate the biosafety of this vaccine to warrant future clinical testing. Thus, these studies will show that our oral/nasal vaccine can protect against Brucella challenges in two different experimental animal models.

描述（由适用提供）：高度感染力的革兰氏阴性布鲁氏菌仍然是全球健康的威胁，是疾病，布鲁氏菌病。在人类中，脑状芽孢杆菌是尽管有侵略性的抗生素治疗，但仍然可以导致后遗症反复出现，以作为波浪发烧和关节炎。宿主内的布鲁氏菌存活与逃避细胞内识别的能力有关，即允许它们在不同时期进行隔离。可以概括布鲁氏菌感染方面的疫苗应证明有效防止感染。因此，我们假设一种模仿天然粘膜芽孢杆菌感染方面的疫苗，能够通过产生TNF-A和IFN-G刺激细胞介导的免疫力，以防止粘膜和全身性布鲁氏菌挑战。为了实现这种方法，我们最近开发了一种疫苗原型，在大多数情况下，在脾或肺中没有可检测到的布鲁氏菌的情况下可以承认完全保护。鉴于该疫苗的效力，我们建议使用两种动物模型来检验假设，以确定该疫苗对野生型B. Melitensis挑战的效率。特定目标1中的研究将建立粘膜（口服，鼻，口服 +鼻）免疫抑制策略，以保护对甲状腺芽孢杆菌和异源布鲁氏菌规范。特定目标2中的研究将在山羊中建立类似的粘膜免疫抑制策略，山羊是梅利氏芽孢杆菌的自然宿主，以防止会议保护 B.梅利辛诱导的流产。特定目标3中的研究将评估该疫苗的生物安全，以保证将来的临床测试。这是这些研究将表明，我们的口服/鼻疫苗可以在两个不同的实验动物模型中预防布鲁氏菌挑战。