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

doi:10.1038/s41541-020-00265-5

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

NPJ Vaccines. 2021 Jan 4;6(1):1. doi: 10.1038/s41541-020-00265-5.

Authors

Youdong Pan¹, Luzheng Liu¹, Tian Tian¹, Jingxia Zhao^{1

2}, Chang Ook Park¹, Serena Y Lofftus¹, Claire A Stingley¹, Yu Yan¹, Shenglin Mei³, Xing Liu⁴, Thomas S Kupper^{5

6}

Affiliations

¹ Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
² Beijing Institute of Traditional Chinese Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China.
³ Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA.
⁴ The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
⁵ Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. tkupper@bwh.harvard.edu.
⁶ Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts, USA. tkupper@bwh.harvard.edu.

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.

Abstract

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