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针对重组和减毒活带状疱疹疫苗产生抗体依赖性细胞毒性的情况

Development of antibody-dependent cellular cytotoxicity in response to recombinant and live-attenuated herpes zoster vaccines.

作者信息

Park Seong Yeon, Levin Myron J, Canniff Jennifer, Johnson Michael, Schmid D Scott, Weinberg Adriana

机构信息

Department of Infectious Diseases, Dongguk University Ilsan Hospital, Goyang, Republic of Korea.

Departments of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.

出版信息

NPJ Vaccines. 2022 Oct 25;7(1):123. doi: 10.1038/s41541-022-00545-2.

DOI:10.1038/s41541-022-00545-2
PMID:36284110
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9593992/
Abstract

Zoster vaccines generate antibody responses against varicella-zoster virus (VZV). We compared antibody-dependent cell cytotoxicity (ADCC) elicited by zoster vaccine live (ZVL) and recombinant zoster vaccine (RZV). ADCC mediated by antibodies against VZV lysate (VZV-ADCC) and recombinant glycoprotein E (gE-ADCC) was measured using plasma from 20 RZV- and 20 ZVL-recipients, including half 50-60-years-old and half ≥70-years-old. Solid phase-bound anti-VZV antibodies stimulated TNFα in NK cells as measured by flow cytometry or ELISA. VZV-ADCC pre- and post-immunization was higher in younger vaccinees. ZVL did not appreciably increase VZV-ADCC, whereas RZV increased VZV-ADCC in older vaccinees. ELISA-measured gE-ADCC was similar across groups pre-immunization; significantly increased after ZVL; and RZV and was higher in younger RZV than ZVL recipients. IgG3 antibodies increased after RZV and ZVL, with greater anti-gE than anti-VZV responses. Moreover, gE-ADCC strongly correlated with anti-gE antibody avidity, but there were no appreciable correlations between VZV-ADCC and avidity. NK cells stimulated by anti-gE antibodies showed increased IFNγ and CD107a expression, which was not observed with anti-VZV antibodies. In conclusion, anti-gE antibodies generated more robust ADCC than anti-VZV antibodies. RZV induced higher ADCC antibodies than ZVL depending on the antigen and age of vaccinees. Older adults had lower ADCC antibodies before and after vaccination than younger adults.

摘要

带状疱疹疫苗可产生针对水痘-带状疱疹病毒(VZV)的抗体反应。我们比较了减毒活带状疱疹疫苗(ZVL)和重组带状疱疹疫苗(RZV)引发的抗体依赖性细胞毒性(ADCC)。使用来自20名RZV接种者和20名ZVL接种者的血浆,测量了针对VZV裂解物(VZV-ADCC)和重组糖蛋白E(gE-ADCC)的抗体介导的ADCC,其中包括一半年龄在50至60岁之间,另一半年龄≥70岁。通过流式细胞术或ELISA测量,固相结合的抗VZV抗体刺激NK细胞产生肿瘤坏死因子α(TNFα)。年轻接种者免疫前后的VZV-ADCC更高。ZVL并未显著增加VZV-ADCC,而RZV在老年接种者中增加了VZV-ADCC。ELISA测量的gE-ADCC在免疫前各组之间相似;ZVL接种后显著增加;RZV接种后也增加,且年轻的RZV接种者中的gE-ADCC高于ZVL接种者。RZV和ZVL接种后IgG3抗体均增加,抗gE反应比抗VZV反应更强。此外,gE-ADCC与抗gE抗体亲和力密切相关,但VZV-ADCC与亲和力之间没有明显相关性。抗gE抗体刺激的NK细胞显示干扰素γ(IFNγ)和CD107a表达增加,而抗VZV抗体刺激则未观察到这种情况。总之,抗gE抗体产生的ADCC比抗VZV抗体更强。根据接种者的抗原和年龄,RZV诱导的ADCC抗体高于ZVL。老年人接种前后的ADCC抗体低于年轻人。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86fb/9596400/70421b4418dd/41541_2022_545_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86fb/9596400/6a9a7a6f1bbc/41541_2022_545_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86fb/9596400/9f3b793b0e8e/41541_2022_545_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86fb/9596400/70421b4418dd/41541_2022_545_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86fb/9596400/6a9a7a6f1bbc/41541_2022_545_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86fb/9596400/4a73c0a0f2f2/41541_2022_545_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86fb/9596400/3b9f4f124a3c/41541_2022_545_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86fb/9596400/9f3b793b0e8e/41541_2022_545_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86fb/9596400/70421b4418dd/41541_2022_545_Fig5_HTML.jpg

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