Vaccine Infection T cell Comparison

Protection from pathogens relies on both humoral (antibody-mediated) and cellular (T cell-mediated) responses. While infections robustly elicit both of these types of immunity, currently approved vaccine adjuvants largely fail to induce significant T cell responses. However, recent work by our lab and others suggests that the mechanisms governing vaccine-elicited T cells (Tvac) may be substantially different than those governing infection-elicited T cells (Tinf). We have recently demonstrated that optimal subunit vaccine-elicited T cell responses rely on different cytokine signals (IL-27 and 15) and metabolic function (oxidative phosphorylation vs. aerobic glycolysis) leading to phenotypically and functionally different outcomes (memory vs. effector). Our goal was to investigate the transcriptional programming that promotes Tvac formation. Using a bulk RNAsequencing approach we compared WT Tvac at day 3 post immunization to Tvac where IL-27 or IL-15 signaling was absent, to Tinf at day 4 post infectious challenge, or to naive OT-1 T cells. A small number (20000) of congenically marked (CD45.1) WT or IL27R KO OT-I T cells were adoptively transferred into WT or IL-15KO naïve B6 recipients (CD45.2). These recipients were then immunized intravenously (i.v.) against OVA using our combined adjuvant vaccine (poly I:C, anti-CD40) or infection with LM-OVA ) or Vaccinia Virus-OVA (VV). OT-I T cells were isolated on day 3 (adjuvant samples) or day 4(infectious samples) post immunization using FACS sorting of CD45.1+ CD8+ cells.