Submitted to: Conference Research Workers Disease Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 9/25/2021
Publication Date: N/A
Technical Abstract: Percutaneous (PC) administration of Bacillus Calmette-Guerin (BCG) is the only approved route of vaccination in humans and has been used in cattle. However, intravenous (IV) BCG vaccination enhanced protection against tuberculosis above PC vaccination routes in rhesus macaques. BCG administration in humans can induce innate memory as well as adaptive memory. Various routes of BCG inoculation in pigs were assessed for induction of innate memory, and adaptive immune responses also assessed to confirm BCG exposure. Of note, an inverse relationship between induction of innate memory and adaptive memory was noted. Four-wk-old pigs were inoculated by subcutaneous (SQ), intramuscular (IM), or IV route with BCG or saline (noBCG – control pigs). A sample size of 8-10 pigs/treatment for each study was maintained. To assess adaptive immune responses, at 5-8 weeks post-inoculation (wpi), ex vivo peripheral blood mononuclear cell (PBMC) IFN' responses to PPD bovine (PPDb) were measured by ELISA. Innate memory was assessed at 2-8 wpi by culturing monocytes with LPS and measuring TNF production. At 6 wpi, inoculation site (SQ group) and liver (SQ and IV groups) samples were collected for BCG culture. PBMC IFN' production following ex vivo PPDb stimulation was increased in SQ and IM groups (5.1 and 3.6-fold, respectively), but not in IV inoculated pigs. Conversely, TNF production from monocytes isolated from IV inoculated pigs and stimulated with LPS was heightened over SQ and IM groups (3.9 fold). However, BCG was recovered from the site of SQ inoculation and liver of IV but not SQ pigs. The lack of peripheral adaptive immune responsiveness following IV but not SQ or IM inoculation along with the converse enhancement of innate immune responses suggests that how or where an antigen is presented to the immune system plays a critical role in the type of immune response generated. In addition, the recovery of BCG from organs of animals with enhanced innate responses calls into question whether constant exposure to BCG or true cellular changes are associated with innate memory.