Ludwig B, Kraus F B, Allwinn R, Keim S, Doerr H W, Buxbaum S
Institute for Medical Virology, Johann Wolfgang Goethe University Frankfurt, Paul-Ehrlich-Str. 40, 60596, Frankfurt a.M., Germany.
Infection. 2006 Aug;34(4):222-6. doi: 10.1007/s15010-006-5616-9.
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.
2004年7月，德国柏林罗伯特·科赫研究所的“常设疫苗接种委员会”（STIKO）建议对儿童进行水痘带状疱疹病毒（VZV）疫苗接种。由于这一建议，医生和实验室将更频繁地面临血清学无应答者或体液免疫丧失的问题。
在此，我们报告一例VZV疫苗接种者的病例，尽管她持续存在VZV特异性CD4细胞免疫应答，但检测不到VZV抗体。我们将这些参数与VZV血清阴性和血清阳性健康人以及VZV疾病患者的VZV特异性CD4 T细胞应答进行比较。
VZV抗体血清阴性者的VZV特异性CD4频率平均低于0.1%（中位数0.04%，±标准差0.03，范围0.01 - 0.08%），显著低于血清阳性健康人的VZV特异性频率（中位数0.3%，±标准差0.24，范围0.06 - 0.81%；曼-惠特尼U检验p = 0.001）。VZV相关疾病患者的样本显示，VZV特异性CD4细胞应答的中位数水平甚至高于VZV血清阳性健康人（中位数1.04%，±标准差1.06，范围0.51 - 2.92%，曼-惠特尼U检验p = 0.008）。医护人员接种疫苗后直接的VZV特异性免疫应答与VZV血清阳性健康成年人的VZV特异性免疫相当。尽管1.5年后血清学发生了转换，但VZV特异性CD4应答仍可测量且呈阳性。
德国针对儿童的新的VZV疫苗接种总体建议可能会增加接种后血清阴性者的数量。为了获得更多关于血清转化缺失或免疫丧失的信息，未来VZV疫苗接种后免疫研究不仅有必要关注血清学检测，还需关注细胞介导免疫的测量。
