Impaired immune response to vaccinia virus inoculated at the site of cutaneous allergic inflammation

BackgroundPatients with atopic dermatitis (AD) exposed to the vaccinia virus (VV) smallpox vaccine have an increased risk of developing eczema vaccinatum.ObjectiveTo investigate the effects of local allergic skin inflammation on vaccinia immunity.MethodsBALB/c mice were epicutaneously sensitized with ovalbumin (OVA) to induce allergic skin inflammation or with saline control, then inoculated with an attenuated VV strain by skin scarification or intraperitoneally. After 8 days, serum IgG anti-VV and cytokine secretion by splenocytes were measured.ResultsMice inoculated with VV at sites of epicutaneous sensitization with OVA, but not control mice inoculated at saline exposed sites, developed satellite pox lesions and had impaired secretion of TH1 cytokines in response to VV, decreased VV specific serum IgG2a, increased VV specific serum IgG1, and impaired upregulation of IFN-α, but not the cathelicidin-related antimicrobial peptide, at the infection site. The VV immune response of OVA-sensitized mice inoculated with VV at distant skin sites or intraperitoneally was normal.ConclusionLocal immune dysregulation at sites of allergic skin inflammation underlies the impaired TH1 immune response to VV introduced at these sites and the increased susceptibility to develop satellite pox lesions, a characteristic of eczema vaccinatum in patients with AD.Clinical implicationsIn a mouse model of AD, inoculation of VV at inflamed skin sites is associated with increased numbers of satellite pox lesions and an abnormal immune response to the virus. This may contribute to the susceptibility of patients with AD to virus dissemination after smallpox vaccination.