Minipigs as animal model for infant TB and vaccine efficacy

小型猪作为婴儿结核病和疫苗功效的动物模型

• 批准号: 8810222
• 负责人: Mercedes Gonzalez-Juarrero
• 金额: $ 18.59万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8810222
• 关键词: Address; Adult; Aerosols; Affect; Animal Model; Animals; Antibodies; Antigens; Area; Bacillus (bacterium); Bacteria; Biological Assay; Biological Markers; Birth; Blood specimen; Body Temperature; Breeding; Child Nutrition; Childhood; Colorado; Communicable Diseases; Coughing; Development; Diagnosis; Diagnostic; Diagnostic radiologic examination; Disease; Disease Progression; Dose; Environment; Family suidae; Flow Cytometry; Genes; Genetic; Genus Mycobacterium; Goals; Goat; Graft Rejection; Health; Human; Immune response; Immunity; Immunologic Tests; Immunologics; Immunology; Infant; Infection; Inflammation; Inflammatory; Intervention; Laboratories; Laboratory Research; Learning; Leukocytes; Life; Liquid substance; Litter Size; Measures; Medical; Miniature Swine; Modeling; Monitor; Mycobacterium tuberculosis; Neonatal; Nose; Organ Transplantation; Outcome Study; Pathologic; Prevention; Protocols documentation; Reagent; Reporting; Reproductive Immunology; Research; Research Personnel; Resources; Route; Sampling; Serum; Socialization; South Africa; Stress; Symptoms; Testing; Toxicology; Tuberculosis; Tuberculosis Vaccines; Universities; Urine; Vaccinated; Vaccination; Vaccines; Virulent; Weight; Work; acid fast bacteria; biosafety level 3 facility; comparative; cytokine; efficacy testing; efficacy trial; experience; high risk; immunopathology; improved; novel strategies; oncology; pregnant; prevent; public health relevance; research facility; response; transmission process; vaccination against tuberculosis; vaccine efficacy; vaccine evaluation

DESCRIPTION (provided by applicant): Four months ago, in February of 2013 the results from one of the largest tuberculosis (TB) vaccine efficacy trial in infants were reported. The trai tested the capacity of M. bovis Bacille Calmette Guerin (BCG) prime -MVA85A boosting to protect infants against TB. One of the lessons learnt from this trail was that there is an urgent need for a different approach to test vaccine efficacy against infant and childhood TB. Today, there are several animal models to test TB vaccine efficacy but there are no animal models to address infant TB, less so animal models to test vaccines and diagnostics for infants. In view of this scenario, in this application we propose to develop an animal model to study infant TB and TB vaccine efficacy testing using adult and piglet minipigs. Our long term goal is to develop a high burden setting formed by adult minipigs affected with TB and vaccinated piglets that will allow to study infant TB and TB vaccine efficacy, biomarker of TB disease and TB transmission. However, to achieve our long term goal, we first need to demonstrate that minipigs (adult and piglets) develop TB disease when infected by aerogenic route with Mycobacterium tuberculosis. Further, we need to demonstrate that vaccination of neonatal piglets with BCG results in the development of similar immunity against TB as that seen in infants. We will also need to address whether there are potential biomarkers in urine and sera of TB diseased piglets that could be used to diagnose infant TB. If successful, the minipig animal setting proposed in these studies will facilitate the understanding of infant TB and its diagnosis, as well as improve the choice of vaccines to be used in childhood TB prevention. The outcomes of the studies proposed here will be documented using comprehensive bacteriologic, immunologic, pathologic approaches now routine in our laboratory. The Mycobacteria Research Laboratories at Colorado State University are uniquely equipped with state-of-the-art BSL-III research facilities to develop these studies. For the purposes of these studies we have assembled a team of highly experienced researchers in the fields of swine immunology, animal models of TB infection, vaccine efficacy testing and biomarkers of TB disease located at Colorado State University and the ARS-USDA.

描述（由申请人提供）：四个月前，2013年2月，报告了婴儿中最大的结核病（TB）疫苗疗效试验的结果。 Trai测试了Bovis M. bacille Calmette Guerin（BCG）Prime -MVA85A的能力，以保护婴儿免受结核病的侵害。从这条小径中学到的经验之一是，迫切需要采取不同的方法来测试针对婴儿和儿童结核病的疫苗功效。如今，有几种可以测试结核病疫苗功效的动物模型，但是没有动物模型可以解决婴儿结核病，较少的动物模型可以测试婴儿的疫苗和诊断。鉴于这种情况，在此应用中，我们建议开发一种动物模型，以使用成人和小猪粉刺研究婴儿结核病和结核病疫苗疗效测试。我们的长期目标是发展由TB和疫苗接种仔猪影响的成年小型ii形成的高负担设置，这些烟草将允许研究婴儿结核病和结核病疫苗疗效，结核病疾病的生物标志物和结核病传播。但是，为了实现我们的长期目标，我们首先需要证明在通过结核分枝杆菌感染的充气途径感染时，米蒂吉（成人和小猪）会出现结核病疾病。此外，我们需要证明，具有BCG的新生儿小猪的疫苗接种会导致对TB的相似免疫力的发展，如婴儿所见。我们还需要解决可以用来诊断婴儿结核病的结核病患病和血清中潜在的生物标志物。如果成功，这些研究中提出的Minipig动物环境将有助于对婴儿结核病及其诊断的理解，并改善用于预防儿童结核病的疫苗的选择。这里提出的研究的结果将使用我们实验室中的综合细菌学，免疫学，病理学方法进行记录。科罗拉多州立大学的分枝杆菌研究实验室具有最先进的BSL-III研究设施，可以开发 这些研究。出于这些研究的目的，我们组建了一个在猪免疫学领域，结核病感染的动物模型，疫苗疗效测试的动物模型以及位于科罗拉多州立大学和ARS-USDA的结核病疾病的生物标志物的团队。

项目成果

Neonatal and infant immunity for tuberculosis vaccine development: importance of age-matched animal models.

• DOI: 10.1242/dmm.045740
• 发表时间: 2020-09-15
• 期刊: Disease models & mechanisms
• 影响因子: 4.3
• 作者: Ramos L;Lunney JK;Gonzalez-Juarrero M
• 通讯作者: Gonzalez-Juarrero M

The minipig as an animal model to study Mycobacterium tuberculosis infection and natural transmission.

• DOI: 10.1016/j.tube.2017.07.003
• 发表时间: 2017-09
• 期刊: Tuberculosis (Edinburgh, Scotland)
• 作者: Ramos L;Obregon-Henao A;Henao-Tamayo M;Bowen R;Lunney JK;Gonzalez-Juarrero M
• 通讯作者: Gonzalez-Juarrero M

Minipigs as a neonatal animal model for tuberculosis vaccine efficacy testing.

小型猪作为结核疫苗功效测试的新生动物模型。

• DOI: 10.1016/j.vetimm.2019.109884
• 发表时间: 2019
• 期刊: Veterinary immunology and immunopathology
• 影响因子: 1.8
• 作者: Ramos,Laylaa;Obregon-Henao,Andres;Henao-Tamayo,Marcela;Bowen,Richard;Izzo,Angelo;Lunney,JoanK;Gonzalez-Juarrero,Mercedes
• 通讯作者: Gonzalez-Juarrero,Mercedes