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中国全国性奥密克戎浪潮后 SARS-CoV-2 免疫反应的异质性。

Heterogeneity of SARS-CoV-2 immune responses after the nationwide Omicron wave in China.

机构信息

Department of Respiratory, Critical Care and Sleep Medicine, School of Medicine, Xiamen University, Xiang'an Hospital of Xiamen University, Xiamen, Fujian, China.

Institute of Chest and Lung Diseases, Xiang'an Hospital of Xiamen University, Xiamen, Fujian, China.

出版信息

Microbiol Spectr. 2024 Nov 5;12(11):e0111724. doi: 10.1128/spectrum.01117-24. Epub 2024 Sep 17.

DOI:10.1128/spectrum.01117-24
PMID:39287459
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11536994/
Abstract

It remains unclear how previous infections and vaccinations influenced and shaped heterogeneous immune responses against Omicron and its variants in diverse populations in China. After the national wave of Omicron in early 2023, we evaluated serum levels of neutralizing antibodies (nAbs) against Omicron (B.1.1.529) and its variants (BA.5, BF.7, and CH1.1) in 33 COVID-19 convalescents and 40 uninfected vaccinees, using vesicular stomatitis virus-based pseudovirus neutralizing assay. In addition, we followed 34 Delta convalescent patients to compare their immune responses against Omicron before (late 2021) and after the Omicron wave (early 2023). NAbs at the acute phase of the disease were investigated in 50 Omicron inpatients, including 24 vaccinated and 26 unvaccinated patients. Among them, nasal mucosal IgA levels were measured in 42 subjects. Compared to vaccination, breakthrough infections significantly increased the breadth and magnitude of serum nAbs and mucosal IgA levels against Omicron variants. Exposure to Omicron but not Delta elicited stronger pan-Omicron responses. In Omicron inpatients, nAbs continued to rise as vaccination doses increased. However, in both vaccinees and convalescents, a fourth dose vaccination did not elicit higher nAbs against Omicron. Furthermore, nAbs against Omicron variants lasted longer than nAbs against WT SARS-CoV-2. Breakthrough infections of Omicron variants elicited specific immune responses against Omicron compared to vaccination and Delta infection. Although repeated vaccination revealed limited impacts on serum nAbs, populations at high risk of hospitalization may still benefit from continued vaccination.IMPORTANCEThe study described the specific humoral immunity against Omicron and its variants (BA.5, BF.7, and CH1.1) in diverse populations, including Delta-positive convalescent patients, Omicron-infected patients with a previous or current confirmed Delta infection, Omicron-positive patients, and healthy controls. In addition, we followed Delta convalescents for 1 year to evaluate the effect of a booster vaccine, breakthrough infection, and reinfection. Nasal mucosal IgA levels against SARS-CoV-2 were also examined. The findings of this study demonstrated the varied responses of individuals in different states following the outbreak of Omicron, highlighting the potential advantages of ongoing immunization for groups that are more vulnerable and have a greater likelihood of being hospitalized.

摘要

目前尚不清楚先前的感染和疫苗接种如何影响和塑造中国不同人群对奥密克戎及其变体的异质性免疫反应。在 2023 年初全国奥密克戎浪潮之后,我们使用基于水疱性口炎病毒的假病毒中和测定法,评估了 33 名 COVID-19 恢复期患者和 40 名未感染疫苗接种者对奥密克戎(B.1.1.529)及其变体(BA.5、BF.7 和 CH1.1)的血清中和抗体(nAb)水平。此外,我们随访了 34 名德尔塔恢复期患者,以比较他们在奥密克戎浪潮之前(2021 年末)和之后(2023 年初)对奥密克戎的免疫反应。我们还在 50 名奥密克戎住院患者中研究了疾病急性期的 nAb,其中包括 24 名接种疫苗的患者和 26 名未接种疫苗的患者。其中,42 名患者测量了鼻黏膜 IgA 水平。与接种疫苗相比,突破性感染显著增加了血清 nAb 和鼻黏膜 IgA 水平对奥密克戎变体的广度和幅度。接触奥密克戎而非德尔塔引发了更强的泛奥密克戎反应。在奥密克戎住院患者中,随着疫苗接种剂量的增加,nAb 持续升高。然而,在疫苗接种者和恢复期患者中,第四剂疫苗接种并未引起针对奥密克戎的更高 nAb。此外,针对奥密克戎变体的 nAb 持续时间长于针对 WT SARS-CoV-2 的 nAb。与接种疫苗和德尔塔感染相比,奥密克戎变体的突破性感染引发了针对奥密克戎的特异性免疫反应。尽管重复接种疫苗对血清 nAb 的影响有限,但住院风险较高的人群可能仍受益于持续接种疫苗。

重要的是,该研究描述了针对奥密克戎及其变体(BA.5、BF.7 和 CH1.1)的不同人群中的特定体液免疫,包括德尔塔阳性恢复期患者、先前或当前确诊的德尔塔感染的奥密克戎感染患者、奥密克戎阳性患者和健康对照者。此外,我们对德尔塔恢复期患者进行了 1 年的随访,以评估加强疫苗接种、突破性感染和再感染的效果。还检查了针对 SARS-CoV-2 的鼻黏膜 IgA 水平。这项研究的结果表明,奥密克戎爆发后不同状态下个体的反应各不相同,这突显了持续免疫接种对更脆弱且更有可能住院的人群的潜在优势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bbd/11536994/be2b90a55f1b/spectrum.01117-24.f006.jpg
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