The Journal of Allergy and Clinical Immunology
Volume 120, Issue 6 , Pages 1382-1388, December 2007

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

  • Jordan E. Scott, MD

      Affiliations

    • Department of Pediatrics, Division of Allergy and Immunology, Children's Hospital, Harvard Medical School, Boston, Mass
    • These authors contributed equally to this work.
    • ,
  • Abdallah ElKhal, PhD

      Affiliations

    • Department of Pediatrics, Division of Allergy and Immunology, Children's Hospital, Harvard Medical School, Boston, Mass
    • These authors contributed equally to this work.
    • ,
  • Eva-Jasmin Freyschmidt, PhD

      Affiliations

    • Department of Pediatrics, Division of Allergy and Immunology, Children's Hospital, Harvard Medical School, Boston, Mass
    • ,
  • Daniel H. MacArthur, BS

      Affiliations

    • Department of Pediatrics, Division of Allergy and Immunology, Children's Hospital, Harvard Medical School, Boston, Mass
    • ,
  • Douglas McDonald, MD, PhD

      Affiliations

    • Department of Pediatrics, Division of Allergy and Immunology, Children's Hospital, Harvard Medical School, Boston, Mass
    • ,
  • Michael D. Howell, PhD

      Affiliations

    • National Jewish Medical and Research Center, Denver, Colo
    • ,
  • Donald Y.M. Leung, MD, PhD

      Affiliations

    • National Jewish Medical and Research Center, Denver, Colo
    • ,
  • Amale Laouar, PhD

      Affiliations

    • Center for Blood Research, Institute for Biomedical Research, Harvard Medical School, Boston, Mass
    • ,
  • N. Manjunath, PhD

      Affiliations

    • Center for Blood Research, Institute for Biomedical Research, Harvard Medical School, Boston, Mass
    • ,
  • Teresa Bianchi, PhD

      Affiliations

    • Brigham and Women's Hospital and Department of Pediatrics and Dermatology, Harvard Medical School, Boston, Mass
    • ,
  • Marianne Boes, PhD

      Affiliations

    • Brigham and Women's Hospital and Department of Pediatrics and Dermatology, Harvard Medical School, Boston, Mass
    • ,
  • Hans C. Oettgen, MD, PhD

      Affiliations

    • Department of Pediatrics, Division of Allergy and Immunology, Children's Hospital, Harvard Medical School, Boston, Mass
    • ,
  • Raif S. Geha, MD

      Affiliations

    • Department of Pediatrics, Division of Allergy and Immunology, Children's Hospital, Harvard Medical School, Boston, Mass
    • Corresponding Author InformationReprint requests: Raif S. Geha, MD, Division of Immunology, Karp 10th floor, One Blackfan Street, Boston, MA 02115.

Received 9 April 2007; received in revised form 30 July 2007; accepted 1 August 2007. published online 24 September 2007.

Background

Patients with atopic dermatitis (AD) exposed to the vaccinia virus (VV) smallpox vaccine have an increased risk of developing eczema vaccinatum.

Objective

To investigate the effects of local allergic skin inflammation on vaccinia immunity.

Methods

BALB/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.

Results

Mice 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.

Conclusion

Local 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 implications

In 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.

Key words: Eczema vaccinatum, allergy, vaccinia virus, smallpox vaccination, viral response, TH1/TH2 cells

Abbreviations used: AD, Atopic dermatitis, CRAMP, Cathelicidin-related antimicrobial peptide, DC, Dendritic cell, DMEM, Dulbecco modified Eagle medium, EV, Eczema vaccinatum, LN, Lymph node, OVA, Ovalbumin, pDC, Plasmacytoid dendritic cell, PFU, Plaque-forming unit, VV, Vaccinia virus

 

 Supported by federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract number HHSN266200400030C (Atopic Dermatitis Vaccinia Network).

 Disclosure of potential conflict of interest: J. Scott has consulting arrangements with Alicare Medical Management, owns Pharmaceutical holder trust stock, and is on the speakers' bureau for Verus Pharmaceuticals. The rest of the authors have declared that they have no conflict of interest.

PII: S0091-6749(07)01457-1

doi:10.1016/j.jaci.2007.08.004

The Journal of Allergy and Clinical Immunology
Volume 120, Issue 6 , Pages 1382-1388, December 2007