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重复变异株暴露对SARS-CoV-2疫苗诱导的细胞免疫原性和体液免疫原性的影响。

Impact of Repeated Variant Exposures on Cellular and Humoral Immunogenicity Induced by SARS-CoV-2 Vaccines.

作者信息

Fernández-Ciriza Leire, Del Pozo José Luis, Betanzos Nazaret, González Álvaro, Fernandez-Montero Alejandro, Carmona-Torre Francisco, Vidaurreta Marta, Carlos Silvia, Reina Gabriel

机构信息

Department of Microbiology, Clínica Universidad de Navarra, 31008 Pamplona, Spain.

Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain.

出版信息

Vaccines (Basel). 2024 Dec 13;12(12):1408. doi: 10.3390/vaccines12121408.

DOI:10.3390/vaccines12121408
PMID:39772069
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11680034/
Abstract

BACKGROUND/OBJECTIVES: The emergence of the Omicron variant has complicated COVID-19 control and prompted vaccine updates. Recent studies have shown that a fourth dose significantly protects against infection and severe disease, though long-term immunity data remain limited. This study aimed to assess Anti-S-RBD antibodies and interferon-γ levels in healthcare workers 12 months after receiving bivalent Original/Omicron BA.4-5 fourth SARS-CoV-2 vaccine.

METHODS

In this prospective cohort study, 549 healthcare workers were categorized by the initial vaccination schedule, with 229 individuals having received the fourth SARS-CoV-2 vaccine dose. Blood samples were collected from all participants 12 months post-vaccination.

RESULTS

Significant differences in Anti-S-RBD antibody levels were observed between those receiving a fourth dose and those who did not, while no differences were seen in interferon-γ levels. After 12 months, there were no significant differences in humoral and cellular immunity response between volunteers primoinfected or reinfected across different periods by the Omicron variant. A multivariable analysis revealed an association between high antibody levels (>6000 U/mL) and interferon-γ levels (OR: 3.13; 95% CI: 1.3-7.7; < 0.05). Regarding primary vaccine schedules, participants vaccinated with ChAdOx1 (a single or double dose) had notably lower antibody levels compared to those who received mRNA-based vaccines. Additionally, the study shows a higher frequency of multiple infections among those with a single-dose ChAdOx1 primary schedule (OR: 6.24; 95% CI: 1.25-31.15; < 0.01).

CONCLUSIONS

Overall, mRNA-based vaccines exhibited stronger long-term immunogenicity. Repeated exposure to the Omicron variant seems to mitigate immune imprinting from the wild-type SARS-CoV-2. An association was observed between high antibody levels and a strong cellular response, although the correlation was not linear.

摘要

背景/目的:奥密克戎变种的出现使新冠疫情防控变得复杂,并促使疫苗更新。近期研究表明,第四剂疫苗能显著预防感染和重症,不过长期免疫数据仍然有限。本研究旨在评估医护人员接种二价原始株/奥密克戎BA.4-5第四剂新冠疫苗12个月后的抗刺突蛋白受体结合域(Anti-S-RBD)抗体和干扰素-γ水平。

方法

在这项前瞻性队列研究中,549名医护人员按初始疫苗接种方案进行分类,其中229人接种了第四剂新冠疫苗。在接种疫苗12个月后采集所有参与者的血样。

结果

接种第四剂和未接种第四剂的人员之间,抗刺突蛋白受体结合域抗体水平存在显著差异,而干扰素-γ水平未见差异。12个月后,不同时期初次感染或再次感染奥密克戎变种的志愿者之间,体液免疫和细胞免疫反应无显著差异。多变量分析显示,高抗体水平(>6000 U/mL)与干扰素-γ水平之间存在关联(比值比:3.13;95%置信区间:1.3-7.7;P<0.05)。关于初始疫苗接种方案,与接种基于信使核糖核酸(mRNA)的疫苗的人员相比,接种腺病毒载体牛津疫苗(ChAdOx1,单剂或双剂)的参与者抗体水平显著较低。此外,研究显示,单剂ChAdOx1初始接种方案的人员多次感染的频率更高(比值比:6.24;95%置信区间:1.25-31.15;P<0.01)。

结论

总体而言,基于mRNA的疫苗表现出更强的长期免疫原性。反复接触奥密克戎变种似乎减轻了野生型新冠病毒的免疫印记。高抗体水平与强烈的细胞反应之间存在关联,尽管这种相关性并非线性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1e/11680034/5d362d44f8ab/vaccines-12-01408-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1e/11680034/c01d1928acad/vaccines-12-01408-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1e/11680034/6e951f0f3c4e/vaccines-12-01408-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1e/11680034/5d362d44f8ab/vaccines-12-01408-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1e/11680034/c01d1928acad/vaccines-12-01408-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1e/11680034/6e951f0f3c4e/vaccines-12-01408-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1e/11680034/5d362d44f8ab/vaccines-12-01408-g003.jpg

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