Location: Animal Parasitic Diseases LaboratoryTitle: Neonatal and infant immunity for vaccine development against tuberculosis: importance of age-matched animal models
|RAMOS, LAYLAA - University Of Colorado|
|GONZALEZ-JUARRERO, MERCEDES - Colorado State University|
Submitted to: Disease Models and Mechanisms
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/18/2020
Publication Date: 9/15/2020
Citation: Ramos, L., Lunney, J.K., Gonzalez-Juarrero, M. 2020. Neonatal and infant immunity for vaccine development against tuberculosis: importance of age-matched animal models. Disease Models and Mechanisms. 13: dmm045740. https://doi.org/10.1242/dmm.045740.
Interpretive Summary: Tuberculosis (TB) is a major infectious disease caused by Mycobacterium tuberculosis (Mtb) bacterial infection and results in 1.5 million deaths worldwide each year. Children serve as a disease reservoir but also c=account for 14% of TB deaths. To date, TB control has relied on Bacillus Calmette-Guerin (BCG) vaccination. Efforts to develop new vaccines are underway but testing has focused on adult animal models. This review highlights the importance of neonatal models for vaccine evaluation and emphasizes the value of the piglet model to study neonatal and infant immunity.
Technical Abstract: The mechanisms by which T cell mediated immune responses differ between newborns and adults remain elusive. These unknowns present challenges in vaccine development. The Tuberculosis (TB) research community has openly admitted a vacuum of knowledge about neonatal and pediatric immunity, especially for the functional and phenotypic attributes of Bacillus Calmette-Guerin (BCG) induced memory T cell responses. Although BCG vaccination results in variable efficacy in preventing pulmonary TB during adolescence and adulthood, 80% of endemic TB countries still administer BCG at birth because it protects against disseminated TB in children. As such, new vaccines must work in conjunction with administration of BCG at birth. However, many mysteries still remain about the neonatal immune response elicited by vaccination with BCG. Animal models currently used to study TB vaccines rely on determining vaccine efficacy in adult aged animals; this presents unique challenges when transitioning to human trials in neonates or infants. In this review, we focus on vaccine development in the field of TB and compare the relative utility of animal models used thus far to study neonatal and infant immunity. We hope to encourage the development of neonatal animal models, especially the use of pigs.