High Constitutive Interleukin 10 Level Interferes With the Immune Response to Varicella-Zoster Virus in Elderly Recipients of Live Attenuated Zoster Vaccine

Author:

Gershon Anne A1,Brooks David2,Stevenson Donald D3,Chin William K4,Oldstone Michael B A5,Gershon Michael D6

Affiliation:

1. Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York

2. Princess Margaret Cancer Center, University of Toronto Medical School, Canada

3. Viral-Immunobiology Laboratory, Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, California

4. Allergy, Asthma, Clinical Immunology Clinic, Naval Medical Center Portsmouth, Virginia

5. Division of Allergy and Immunology, Scripps Clinic Medical Group, La Jolla, California

6. Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, New York

Abstract

Abstract Introduction Live attenuated zoster vaccine (Zostavax) was used to test the hypothesis that constitutive level of interleukin 10 (IL-10), which may be high in elderly subjects, impairs vaccine efficacy. If constitutive IL-10 impairs vaccine efficacy, the effectiveness of viral vaccines might be improved by transient inhibition of IL-10 before vaccination. Methods Zostavax was given to 26 patients (age, 60–80 years). IL-10 and immunity to varicella zoster virus (VZV) were measured at baseline and after vaccination. Fluorescent antibody to membrane antigen (FAMA) assays and glycoprotein enzyme-linked immunosorbent assays (gpELISAs) were used to assess humoral immunity; anti–varicella virus T-cell responses were studied in a subset of subjects. In a prospective animal model, T-cell responses to chimeric vaccines against lymphocytic choriomeningitis virus (LCMV) were assessed in mice that express or lack IL-10. Results FAMA assays revealed significant boosting (by 4-fold) of humoral immunity, which occurred only in subjects (10 of 26) with a low constitutive IL-10 level (ie, <20 pg/mL); moreover, the Zostavax-induced FAMA and gpELISA responses were inversely related to the constitutive IL-10 level. Significant VZV-specific T-cell responses followed vaccination only in subjects with a low constitutive IL-10 level. Vaccine-induced LCMV-specific T-cell responses in mice lacking IL-10 were greater than in wild-type animals. Conclusions A high constitutive IL-10 level adversely affects vaccine efficacy.

Funder

Allergy Immunology Fellowship Program

Scripps Research Institute (Green Hospital); and the United States Department of Defense Office of Naval Research (Graduate Education Program)

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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