Epicutaneous immunization with modified vaccinia Ankara viral vectors generates superior T cell immunity against a respiratory viral challenge
Youdong Pan,
Luzheng Liu,
Tian Tian,
Jingxia Zhao,
Chang Ook Park,
Serena Y. Lofftus,
Claire A. Stingley,
Yu Yan,
Shenglin Mei,
Xing Liu,
Thomas S. Kupper
Affiliations
Youdong Pan
Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women’s Hospital, Harvard Medical School
Luzheng Liu
Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women’s Hospital, Harvard Medical School
Tian Tian
Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women’s Hospital, Harvard Medical School
Jingxia Zhao
Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women’s Hospital, Harvard Medical School
Chang Ook Park
Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women’s Hospital, Harvard Medical School
Serena Y. Lofftus
Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women’s Hospital, Harvard Medical School
Claire A. Stingley
Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women’s Hospital, Harvard Medical School
Yu Yan
Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women’s Hospital, Harvard Medical School
Shenglin Mei
Department of Biomedical Informatics, Harvard Medical School
Xing Liu
The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences
Thomas S. Kupper
Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women’s Hospital, Harvard Medical School
Abstract Modified Vaccinia Ankara (MVA) was recently approved as a smallpox vaccine. Variola is transmitted by respiratory droplets and MVA immunization by skin scarification (s.s.) protected mice far more effectively against lethal respiratory challenge with vaccinia virus (VACV) than any other route of delivery, and at lower doses. Comparisons of s.s. with intradermal, subcutaneous, or intramuscular routes showed that MVAOVA s.s.-generated T cells were both more abundant and transcriptionally unique. MVAOVA s.s. 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 s.s. immunization compared to intra-tracheal immunization with MVAOVA and both routes vaccination protected mice against lethal pulmonary challenge with VACVOVA. Strikingly, MVAOVA s.s.-generated effector T cells exhibited overlapping gene transcriptional profiles to those generated via intra-tracheal immunization. Overall, our data suggest that heterologous MVA vectors immunized via s.s. are uniquely well-suited as vaccine vectors for respiratory pathogens, which may be relevant to COVID-19. In addition, MVA delivered via s.s. could represent a more effective dose-sparing smallpox vaccine.
