Pan et al. showed that epicutaneous (skin scarification, s.s.) delivery of modified vaccinia Ankara (MVA), a replication-deficient vaccinia virus (VACV), was safe even in Rag1-/- mice, and was the most effective and dose-sparing route to protect mice against skin or lethal intranasal VACV challenge. S.s. delivery of MVA modified to express OVA generated transcriptionally distinct and more CD8+ TEFF cells than those induced by i.d., s.c., or i.m. delivery. Langerhans cells and CD207+ dermal DCs presented antigen, eliciting specific skin and lung TRM cells and TEFF, TEM, and TCM in lymph nodes and spleen. Lung immunization generated abundant skin TRM cells.
Contributed by Paula Hochman
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 MVA(OVA) s.s.-generated T cells were both more abundant and transcriptionally unique. MVA(OVA) s.s. produced greater numbers of lung Ova-specific CD8(+) T(RM) and was superior in protecting mice against lethal VACV(OVA) respiratory challenge. Nearly as many lung T(RM) were generated with MVA(OVA) s.s. immunization compared to intra-tracheal immunization with MVA(OVA) and both routes vaccination protected mice against lethal pulmonary challenge with VACV(OVA). Strikingly, MVA(OVA) 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.
Author Info: (1) Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. (2) Department of Dermatol
Author Info: (1) Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. (2) Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. (3) Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. (4) Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Beijing Institute of Traditional Chinese Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China. (5) Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. (6) Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. (7) Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. (8) Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. (9) Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA. (10) The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China. (11) Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. tkupper@bwh.harvard.edu. Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts, USA. tkupper@bwh.harvard.edu.
