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Smallpox vaccination induces a substantial increase in commensal skin bacteria that promote pathology and influence the host response.

Published version
Peer-reviewed

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Authors

Gomez de Agüero, Mercedes  ORCID logo  https://orcid.org/0000-0002-7132-290X
Macpherson, Andrew J 

Abstract

Interactions between pathogens, host microbiota and the immune system influence many physiological and pathological processes. In the 20th century, widespread dermal vaccination with vaccinia virus (VACV) led to the eradication of smallpox but how VACV interacts with the microbiota and whether this influences the efficacy of vaccination are largely unknown. Here we report that intradermal vaccination with VACV induces a large increase in the number of commensal bacteria in infected tissue, which enhance recruitment of inflammatory cells, promote tissue damage and influence the host response. Treatment of vaccinated specific-pathogen-free (SPF) mice with antibiotic, or infection of genetically-matched germ-free (GF) animals caused smaller lesions without alteration in virus titre. Tissue damage correlated with enhanced neutrophil and T cell infiltration and levels of pro-inflammatory tissue cytokines and chemokines. One month after vaccination, GF and both groups of SPF mice had equal numbers of VACV-specific CD8+ T cells and were protected from disease induced by VACV challenge, despite lower levels of VACV-neutralising antibodies observed in GF animals. Thus, skin microbiota may provide an adjuvant-like stimulus during vaccination with VACV and influence the host response to vaccination.

Description

Keywords

Research Article, Medicine and health sciences, Biology and life sciences

Journal Title

PLoS Pathog

Conference Name

Journal ISSN

1553-7366
1553-7374

Volume Title

18

Publisher

Public Library of Science (PLoS)
Sponsorship
Wellcome Trust (090315/Z/09/Z)
Medical Research Council (MR/M019810/1)