Location: Animal Parasitic Diseases LaboratoryTitle: Minipigs as neonatal animal model for tuberculosis vaccine efficacy testing
|RAMOS, LAYLAA - Colorado State University|
|OBREGON-HENAO, ANDRES - Colorado State University|
|HENAO-TAMAYO, MARCELA - Colorado State University|
|BOWEN, RICHARD - Colorado State University|
|IZZO, ANGELO - Colorado State University|
|GONZALEZ-JUARRERO, MERCEDES - Colorado State University|
Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/26/2019
Publication Date: 9/1/2019
Citation: Ramos, L., Obregon-Henao, A., Henao-Tamayo, M., Bowen, R., Izzo, A., Lunney, J.K., Gonzalez-Juarrero, M. 2019. Minipigs as neonatal animal model for tuberculosis vaccine efficacy testing. Veterinary Immunology and Immunopathology. 215:109884. https://doi.org/10.1016/j.vetimm.2019.109884.
Interpretive Summary: Background: The only vaccine available against tuberculosis (TB) is Bacillus Calmette-Guerin (BCG). Failure in the development of new pediatric vaccines against TB may be due to incomplete knowledge in the immune response elicited after neonatal vaccination and testing of vaccine efficacy in adults rather than in neonatal animal models. In this novel approach, we used the minipig as a neonatal/infant animal model for evaluation of the immune responses to BCG vaccination. Methods and results: Neonatal minipigs were vaccinated with BCG at 48 hours after birth; thereafter we performed a longitudinal study to characterize T cells, cytokine profiles, and monocyte activation in response to BCG stimulation from 4 weeks (representing infant age in humans) to 24 weeks of age (representing adolescence age in humans). The same monitoring was applied to a group of unvaccinated minipigs. Further, we challenged both vaccinated and non-vaccinated animals via the aerosol route with Mycobacterium tuberculosis (Mtb) strain HN878 and characterized changes in the course of immune responses between the two groups following challenge. Conclusion: Based on comparison of immune responses to BCG in minipigs and infants, our findings suggest that minipigs have the potential to serve as an effective neonatal/infant animal model for TB vaccine development.
Technical Abstract: Numerous groups have attempted to develop vaccines to control human tuberculosis (TB). To date the only vaccine available against TB is Bacillus Calmette-Guerin (BCG). There have been major failures in the development of new pediatric vaccines against TB due to incomplete knowledge of the immune response elicited after neonatal vaccination and to testing vaccine efficacy in adults rather than in neonatal animal models. Our aim was to determine if piglets have similar immunological responses to those found in previous studies of infants vaccinated with BCG. We challenged both vaccinated and non-vaccinated animals via the aerosol route with Mycobacterium tuberculosis (Mtb) and characterized changes in immune responses between the two groups following challenge. By demonstrating a similar course of TB infection and similar immune response to BCG and to Mtb challenge in minipigs, as compared to humans, our results affirm that the pig model can be used for development of diagnostics, drugs and vaccines against TB.