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，即 2013 年 2 月，报告了一项最大的婴儿结核病 (TB) 疫苗功效试验的结果。该试验测试了牛分枝杆菌卡介苗 (BCG) prime -MVA85A 增强剂保护婴儿免受结核病感染的能力。从这次试验中吸取的教训之一是，迫切需要一种不同的方法来测试疫苗对婴儿和儿童结核病的功效。如今，有几种动物模型可以测试结核病疫苗的功效，但没有动物模型可以解决婴儿结核病问题，更不用说动物模型可以测试婴儿的疫苗和诊断方法。鉴于这种情况，在本申请中，我们建议开发一种动物模型来研究婴儿结核病以及使用成年和仔猪小型猪进行结核病疫苗功效测试。我们的长期目标是开发一个由感染结核病的成年小型猪和接种疫苗的仔猪组成的高负担环境，以便研究婴儿结核病和结核病疫苗的功效、结核病和结核病传播的生物标志物。然而，为了实现我们的长期目标，我们首先需要证明小型猪（成年猪和仔猪）在通过气源性途径感染结核分枝杆菌时会患上结核病。此外，我们需要证明，给新生仔猪接种卡介苗可以产生与婴儿相似的结核病免疫力。我们还需要解决患有结核病仔猪的尿液和血清中是否存在可用于诊断婴儿结核病的潜在生物标志物。如果成功，这些研究中提出的小型猪动物环境将有助于了解婴儿结核病及其诊断，并改善用于儿童结核病预防的疫苗的选择。这里提出的研究结果将使用我们实验室目前常规的综合细菌学、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独特地配备了最先进的 BSL-III 研究设施来开发 这些研究。为了进行这些研究，我们在科罗拉多州立大学和 ARS-USDA 组建了一支由猪免疫学、结核感染动物模型、疫苗功效测试和结核病生物标志物领域经验丰富的研究人员组成的团队。

项目成果

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

结核疫苗开发的新生儿和婴儿免疫力：年龄匹配动物模型的重要性。

• 发表时间: 2020-09-15
• 影响因子: 4.3
• 作者: Ramos, Laylaa;Lunney, Joan K;Gonzalez
• 通讯作者: Gonzalez

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。

• 发表时间: 2019-09
• 影响因子: 1.8
• 作者: Ramos, Laylaa;Obregon;Henao;Bowen, Richard;Izzo, Angelo;Lunney, Joan K;Gonzalez
• 通讯作者: Gonzalez

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

以小型猪作为动物模型来研究结核分枝杆菌感染和自然传播。

• DOI: 10.1016/j.tube.2017.07.003
• 发表时间: 2017-09
• 期刊: Tuberculosis
• 影响因子: 3.2
• 作者: Ramos L;Obregon-Henao A;Henao-Tamayo M;Bowen R;Lunney JK;Gonzalez-Juarrero M
• 通讯作者: Gonzalez-Juarrero M