Loss of Varicella Zoster Virus Antibodies Despite Detectable Cell Mediated Immunity after Vaccination

Abstract

Vaccination of children against VZV has been included in the recommendations of the "permanent committee of vaccination" (STIKO; Ständige Impfkommission of the Robert Koch Institute, Berlin, Germany) in July 2004. Due to this recommendation the medical practitioner and the laboratories will be confronted with the problem of serologic non-responders or loss of humoral immunity more frequently. Here we report the case of a Varicella Zoster Virus (VZV) vaccinee, who lost detectable VZV antibodies although she had a persisting VZV specific CD4 cellular immune response. We compare these parameters to the VZV specific CD4 T cell responses of VZV seronegative and seropositive healthy persons, as well as patients with VZV disease. VZV specific CD4 frequencies of VZV antibody seronegative persons remained on the average below 0.1% (median 0.04%, +/- SD 0.03, range 0.01-0.08%) and were significantly lower than VZV specific frequencies of seropositive healthy persons (median 0.3%, +/- SD 0.24, range 0.06-0.81%; Mann-Whitney U-test p = 0.001). The samples of patients with VZV associated disease showed an even higher median level of VZV specific CD4 cell response than the VZV seropositive healthy persons (median 1.04%, +/- SD 1.06, range 0.51-2.92%, Mann-Whitney U-test p = 0.008). The VZV specific immune response of the health care worker directly after vaccination was comparable to the VZV specific immunity in VZV seropositive healthy adults. Despite serological reconversion 1.5 years later the VZV specific CD4 response still remained measurable and positive. The new general VZV vaccination recommendation for children in Germany will probably increase the number of persons that will be seronegative after vaccination. To gain more information concerning the absence of seroconversion or the loss of immunity, it will be necessary to focus future post-VZV vaccination immunity studies not only on serologic testing but also on the measuring of the cell mediated immunity.