Location: Infectious Bacterial Diseases ResearchTitle: Immunology of bovine tuberculosis: Perspectives on one health approaches and defining correlates of protection versus infection
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 8/23/2017
Publication Date: N/A
Technical Abstract: Tuberculosis (TB), primarily due to Mycobacterium tuberculosis in humans and Mycobacterium bovis in cattle, is an exemplary model of the One Health Concept. The human TB vaccine, M. bovis bacille Calmette-Guerin (BCG), was first proven effective in cattle prior to use in humans. Recent experimental trials with cattle have demonstrated that: (1) select attenuated M. bovis mutants provide similar to improved efficacy as BCG, (2) subunit vaccines may be used to augment immunity elicited by BCG in cattle, and (3) differentiation of infected from vaccinated animals (DIVA) is feasible in cattle using both in vitro (IFN-' release assays, developed for use in cattle and now used widely in both humans and cattle) and in vivo (skin test, developed for use in cattle prior to use in humans) methods. Experimental infection / vaccine efficacy studies with cattle have also demonstrated a correlation of vaccine-elicited central memory T cell (TCM) responses with protection upon subsequent challenge with M. bovis. Specifically, higher frequencies of TCM producing IFN-'/TNF-a/IL-2 early after infection are associated with vaccine-elicited protection and bacterial arrest by the host. Using RNA-seq, numerous Th17-associated cytokine genes (including IL-17A, IL-17F, IL-22, IL-19, and IL-27) are up-regulated > 9 fold in response to purified protein derivative stimulation of PBMC from M. bovis-infected cattle, demonstrating a robust induction of these cytokines in tuberculous cattle. Protective vaccines (i.e., BCG and immune-enhancing BCG mutants) also elicit IL-17A, IL-17F, IL-22, and IL-27 responses as measured by rt-PCR in cattle. More importantly, reduced IL-17A responses by vaccinates as compared to non-vaccinates at 2.5 weeks after M. bovis aerosol challenge correlate with reduced mycobacterial (antigen) burden and lesion severity. These findings further characterize the nature of protective TCM responses and demonstrate a correlation of mycobacterial burden on the level of effector CMI responses early after M. bovis infection.