Innate Memory Following Intravenous BCG in Neonatal Pigs

Abstract

Abstract In adults and rodents, Bacillus Calmette-Guerin (BCG) inoculation alters innate immune cells via epigenetic and metabolic modifications resulting in heightened responses to subsequent microbial exposure (innate memory). Neonatal BCG vaccination can correlate to improved disease resistance in some human populations, but studies with human infants are extremely limited. Pigs are a relevant biomedical model for human disease and offer a path to directly asses neonatal innate memory to improve disease resilience. BCG administration in a weaned (3 week old) pig model elicited monocyte memory only with intravenous (IV) but not subcutaneous administration. Therefore, to evaluate induction of innate memory in neonates, 3–5 day old piglets received intravenous (IV) BCG or mock and ex vivo monocyte memory was assessed. At 3 and 6 weeks post-BCG, monocytes from the IV-BCG group had elevated TNF but not IL-1β production in response to LPS stimulation ex vivo, indicating neonatal BCG exposure induced innate memory. Interestingly, broncho-alveolar lavage cells from IV-BCG group had minimal differences compared to mock group in response to LPS, suggesting IV-BCG alters responses in peripheral monocytes differently than tissue resident myeloid-lineage cells. Overall, IV-BCG administration induced monocyte memory in neonatal pigs, highlighting piglets as a valuable model for continued study on the utility of BCG induced innate memory to improve disease resilience. This work was funded by USDA-NIFA AFRI grant # 2019-07511 as part of the joint USDA-NIFA-NIH Dual Purpose with Dual Benefit: Research in Biomedicine and Agriculture Using Agriculturally Important Domestic Animal Species Program and USDA-ARS CRIS project 5030-32000-225-000D