Innate and Adaptive Responses to Bacillus Calmette-Guerin in Young Pigs

Abstract

Development of novel antibiotic alternatives is a critical One Health priority impacting both human and animal wellbeing. While the attenuated strain of M. bovis (Bacillus Calmette-Guerin, BCG) was developed as a vaccine against tuberculosis; recently, BCG has been observed to alter circulating monocytes leading to enhanced inflammatory immune responses to heterologous agonists. These changes can persist for months after the initial BCG exposure, and may serve to enhance innate immune health and reduce disease without the use of antibiotics. Following in vitro observation of innate training in pig monocytes, we wanted to study in vivo BCG responses in pigs as a potential path to enhance innate immunity. Young pigs were inoculated with BCG and weeks later ex vivo cytokine responses to innate TLR agonists and IFNγ response to M. bovis purified protein derivates (PPDb) were measured. PPDb stimulated PBMCs from pigs inoculated subcutaneous with 10⁷ CFU of BCG produced the highest amount of IFNγ as compared to intramuscular inoculated or 10⁶ CFU inoculated pigs. No differences were observed in PBMCs or monocytes stimulated ex vivo with TLR agonists between control and BCG inoculated pigs regardless of route or dose administered. Unlike cattle and humans, in pigs BCG does not seem to readily disseminate from the inoculation site, which may explain the lack of altered innate immune responses observed. Differences in adaptive immune responses indicated alterations to dose or route of BCG administration impacted immunogenicity. Future studies will employ intravenous BCG administration to understand if peripheral exposure to BCG is required to alter innate responses in circulating pig monocytes.