Gene expression profile of OT-I CD8+ T cell subtypes

Modified Vaccinia Ankara (MVA) was recently approved as a Smallpox vaccine. Transmission of Variola is by respiratory droplets, and MVA delivered by skin scarification (ss) protected mice far more effectively against lethal respiratory challenge with VACV than any other route of delivery, and at much lower doses. Comparisons of ss with intradermal, subcutaneous or intramuscular routes showed that MVAOVA ss-generated T cells were both more abundant and transcriptionally distinct. MVAOVA ss produced greater numbers of lung Ova-specific CD8+ TRM and was superior in protecting mice against lethal VACVOVA respiratory challenge. Nearly as many lung TRM were generated with MVAOVA ss compared to direct pulmonary immunization with MVAOVA, and both routes vaccination protected mice against lethal pulmonary challenge with VACVOVA. Strikingly, MVAOVA ss-generated effector T cells exhibited overlapping gene transcriptional profiles to those generated via direct pulmonary immunization. Overall, our data suggest that heterologous MVA vectors delivered via ss are uniquely well-suited as vaccine vectors for respiratory pathogens like COVID-19. In addition, MVA delivered via ss could represent a more effective dose-sparing smallpox vaccine. OT-I naïve T cells, activated OT-I cells, central meory T cells, effector memory T cells were sorted out from mice at different timepoints post 1.8X10-6 MVA infection via indicated infection routes OT-I cells from 15-20 mice were pooled together for each microarray dataset By comparing the gene expression profile among different T cell subtypes, we aimed to identify core regulatory genes differentially expressed in T cell subtypes activated via distinct infection routes (skin scarification, intradermal, subcutaneous, intramuscular, intratracheal,intraperitoneal)