Ag85A-specific CD4+ T cell lines derived after boosting BCG-vaccinated cattle with Ad5-85A possess both mycobacterial growth inhibition and anti-inflammatory properties

Publication date: 11 May 2018
Source:Vaccine, Volume 36, Issue 20
Author(s): Hannah J. Metcalfe, Lucia Biffar, Sabine Steinbach, Efrain Guzman, Tim Connelley, Ivan Morrison, H. Martin Vordermeier, Bernardo Villarreal-Ramos
There is a need to improve the efficacy of the BCG vaccine against human and bovine tuberculosis. Previous data showed that boosting bacilli Calmette-Guerin (BCG)-vaccinated cattle with a recombinant attenuated human type 5 adenovirally vectored subunit vaccine (Ad5-85A) increased BCG protection and was associated with increased frequency of Ag85A-specific CD4⁺ T cells post-boosting. Here, the capacity of Ag85A-specific CD4⁺ T cell lines – derived before and after viral boosting – to interact with BCG-infected macrophages was evaluated. No difference before and after boosting was found in the capacity of these Ag85A-specific CD4⁺ T cell lines to restrict mycobacterial growth, but the secretion of IL-10 in vitro post-boost increased significantly. Furthermore, cell lines derived post-boost had no statistically significant difference in the secretion of pro-inflammatory cytokines (IL-1β, IL-12, IFNγ or TNFα) compared to pre-boost lines. In conclusion, the protection associated with the increased number of Ag85A-specific CD4⁺ T cells restricting mycobacterial growth may be associated with anti-inflammatory properties to limit immune-pathology.



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