Epicutaneous immunization with modified vaccinia Ankara viral vectors generates superior T cell immunity against a respiratory viral challenge

Abstract Modified Vaccinia Ankara (MVA) was recently approved as a smallpox vaccine. Variola is transmitted by respiratory droplets and MVA immunization skin scarification (s.s.) protected mice far more effectively against lethal challenge with vaccinia virus (VACV) than any other route of delivery, at lower doses. Comparisons s.s. intradermal, subcutaneous, or intramuscular routes showed that OVA s.s.-generated T cells were both abundant transcriptionally unique. produced greater numbers lung Ova-specific CD8 + RM superior in protecting VACV challenge. Nearly many generated compared to intra-tracheal vaccination pulmonary . Strikingly, effector exhibited overlapping gene transcriptional profiles those via immunization. Overall, our data suggest heterologous vectors immunized are uniquely well-suited vaccine for pathogens, which may be relevant COVID-19. In addition, delivered could represent effective dose-sparing