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.

Details

Title
Epicutaneous immunization with modified vaccinia Ankara viral vectors generates superior T cell immunity against a respiratory viral challenge
Author
Pan Youdong 1 ; Liu Luzheng 1 ; Tian, Tian 1 ; Zhao, Jingxia 2 ; Park Chang Ook 3   VIAFID ORCID Logo  ; Lofftus, Serena Y 3 ; Stingley, Claire A 3 ; Yu, Yan 3 ; Shenglin, Mei 4 ; Liu, Xing 5 ; Kupper, Thomas S 6   VIAFID ORCID Logo 

1  Brigham and Women’s Hospital, Harvard Medical School, Department of Dermatology and Harvard Skin Disease Research Center, Boston, USA 
2  Brigham and Women’s Hospital, Harvard Medical School, Department of Dermatology and Harvard Skin Disease Research Center, Boston, USA; Capital Medical University, Beijing Institute of Traditional Chinese Medicine, Beijing Hospital of Traditional Chinese Medicine, Beijing, China (GRID:grid.24696.3f) (ISNI:0000 0004 0369 153X) 
3  Brigham and Women’s Hospital, Harvard Medical School, Department of Dermatology and Harvard Skin Disease Research Center, Boston, USA (GRID:grid.24696.3f) 
4  Harvard Medical School, Department of Biomedical Informatics, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
5  Chinese Academy of Sciences, The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai, China (GRID:grid.9227.e) (ISNI:0000000119573309) 
6  Brigham and Women’s Hospital, Harvard Medical School, Department of Dermatology and Harvard Skin Disease Research Center, Boston, USA (GRID:grid.9227.e); Dana-Farber/Brigham and Women’s Cancer Center, Boston, USA (GRID:grid.417747.6) (ISNI:0000 0004 0460 3896) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20590105
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41541-020-00265-5
ProQuest document ID
2474982168
Copyright
© The Author(s) 2021. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.