Location: Infectious Bacterial Diseases ResearchTitle: One health/veterinary links associated with TB vaccines Author
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 3/13/2013
Publication Date: 4/24/2013
Citation: Waters, W.R. 2013. One health/veterinary links associated with TB vaccines [abstract]. Conference on Vaccine Research. Abstract No. 20. Interpretive Summary:
Technical Abstract: Objectives: participants will understand the current status of veterinary tuberculosis (TB) vaccine research for cattle and wildlife and their potential applications for development of human TB vaccines. Vaccines are lacking for many chronic intracellular pathogens requiring cell-mediated immunity for protection. A serious impediment to vaccine discovery is a lack of animal models predictive of efficacy in humans. For TB, vaccine efficacy studies using Mycobacterium tuberculosis in non-human primates (NHPs) offer a logical model for prediction of efficacy in humans. Availability (especially of neonates) and costs associated with BL-3 care, however, hinder widespread use of NHP’s for vaccine testing. Thus, many candidate TB vaccines are tested using mice and guinea pigs; yet, only a few of the vaccines deemed effective with rodent models have emerged for evaluation in Phase 1 human trials. Mycobacterium bovis infection of cattle and relevant wildlife reservoirs results in disease that is similar to M. tb infection in humans. Prior to pasteurization, ~25% of TB cases in humans was attributable to M. bovis. Infection with M. bovis in humans is clinically indistinguishable from M. tb infection and these two organisms have ~99.95% sequence identity. While the mainstay of bovine TB control has been abattoir inspection and targeted antemortem testing, vaccines are being considered as an additional control tool, both for cattle and wildlife reservoirs of bovine TB. Field efficacy trials performed in the early 20th century demonstrated the partial effectiveness of M. bovis Bacillus Calmette Guerin (BCG) for the control of bovine TB. 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 boost immunity elicited by BCG in cattle, (3) BCG is particularly protective when administered to neonates, (4) T cell central memory immune responses evoked by protective vaccines correlate with protection upon subsequent M. bovis challenge, and (5) differentiation of infected from vaccinated animals (DIVA) is feasible in cattle using both in vitro (interferon-gamma release assays) and in vivo (skin test) methods. In regards to wildlife reservoirs, the efficacy of BCG delivered orally has been demonstrated for brushtail possums (in field trials) as well as Eurasian badgers, wild boar, and white-tailed deer (each in experimental challenge studies). In addition to typical efficacy parameters, efforts are on-going to develop experimental biology approaches to evaluate vaccine efficacy based upon reduced transmission, both for cattle and white-tailed deer. Vaccine efficacy trials, particularly field studies and trials evaluating ability of vaccines to limit transmission, with cattle and wildlife reservoirs of bovine TB represent a primary example of the one health approach, with outcomes relevant to both veterinary and medical applications. Reference: 1. Waters, W.R., M. V. Palmer, B. M. Buddle, H. M. Vordermeier. 2012. Bovine tuberculosis vaccine research: historical perspectives and recent advances. Vaccine, 30: 2611-2622.