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.

Public Health Relevance

There is still no effective medical intervention to cure or prevent tuberculosis (TB). The most recent TB vaccine efficacy trial in South Africa revealed that new approaches to study infant and childhood TB are urgently needed. There are no current animal models to study infant TB. Here we propose to develop an animal model to study infant TB, TB vaccine efficacy and biomarkers of TB disease progression using a high burden setting formed by adult minipigs affected with TB and vaccinated piglets.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Exploratory/Developmental Grants (R21)
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Vaccines Against Microbial Diseases Study Section (VMD)
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Eichelberg, Katrin
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Colorado State University-Fort Collins
Schools of Veterinary Medicine
Fort Collins
United States
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Ramos, Laylaa; Obregon-Henao, Andres; Henao-Tamayo, Marcela et al. (2017) The minipig as an animal model to study Mycobacterium tuberculosis infection and natural transmission. Tuberculosis (Edinb) 106:91-98