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Minipigs as a neonatal animal model for TB vaccine efficacy

Date

2016

Authors

Ramos Arriaza, Laylaa, author
Gonzalez-Juarrero, Mercedes, advisor
Bowen, Richard, committee member
Izzo, Angelo, committee member
Guth, Amanda, committee member
Dow, Steven, committee member

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Abstract

Currently, the only vaccine available to prevent tuberculosis (TB) is Bacillus Calmette-Guerin (BCG). The vaccine lacks efficacy against pulmonary disease or reactivation of latent TB but prevents disseminated TB in children and is thus widely used in countries with endemic TB as part of the neonatal vaccine regimen. There are several new vaccines that have shown efficacy against TB in adult animal models yet fail to protect infants from TB disease in clinical trials. Failure in the development of new pediatric vaccines may be due to incomplete knowledge in the elicited immune response to BCG vaccination and testing of vaccine efficacy in adult rather than neonatal animal models. In this novel approach, we used the mini-pig as a neonatal animal model for evaluation of immune responses to BCG vaccine. We demonstrate young mini-pigs are susceptible hosts to the highly virulent Mycobacterium tuberculosis (Mtb) strain, HN878 and that the pathological course of infection resembles that seen in human TB. In this study we longitudinally monitored the immune response of neonatal mini-piglets vaccinated with BCG until adulthood, with the same monitoring applied to a group of unvaccinated mini-piglets. Further, we challenged both vaccinated and non-vaccinated animals via the aerosol route with HN878 and we characterized important changes between the two groups in the course of immune responses following challenge. Based on comparison of immune responses to BCG in mini-pigs and infants, our findings suggest that mini-pigs have the potential to serve as an effective neonatal animal model for TB vaccine development.

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