Smallpox vaccination induces a substantial increase in commensal skin bacteria that promote pathology and enhance immunity

There is growing interest in interactions between pathogens, host microbiota and the immune system, which influence many physiological and pathological processes. Previously, widespread dermal vaccination with vaccinia virus (VACV) led to the eradication of smallpox. 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 increase immunity. 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 mice had reduced VACV-neutralising antibodies; while numbers of VACV-specific CD8+ T cells were equal in all groups of animals. Thus, skin microbiota may provide an adjuvant-like stimulus during vaccination with VACV. This observation has implications for dermal vaccination with live vaccines.