Immunology and Infectious Diseases Program, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland and Labrador, St. John's, NL A1B 3V6, Canada.
Eastern Regional Health Authority, Department of Health and Community Services, St. John's, NL A1B 3V6, Canada.
Viruses. 2023 Apr 18;15(4):996. doi: 10.3390/v15040996.
Some SARS-CoV-2-exposed individuals develop immunity without overt infection. We identified 11 individuals who were negative by nucleic acid testing during prolonged close contact and with no serological diagnosis of infection. As this could reflect natural immunity, cross-reactive immunity from previous coronavirus exposure, abortive infection due to de novo immune responses, or other factors, our objective was to characterize immunity against SARS-CoV-2 in these individuals. Blood was processed into plasma and peripheral blood mononuclear cells (PBMC) and screened for IgG, IgA, and IgM antibodies (Ab) against SARS-CoV-2 and common β-coronaviruses OC43 and HKU1. Receptor blocking activity and interferon-alpha (IFN-α) in plasma were also measured. Circulating T cells against SARS-CoV-2 were enumerated and CD4 and CD8 T cell responses discriminated after in vitro stimulation. Exposed uninfected individuals were seronegative against SARS-CoV-2 spike (S) and selectively reactive against OC43 nucleocapsid protein (N), suggesting common β-coronavirus exposure induced Ab cross-reactive against SARS-CoV-2 N. There was no evidence of protection from circulating angiotensin-converting enzyme (ACE2) or IFN-α. Six individuals had T cell responses against SARS-CoV-2, with four involving CD4 and CD8 T cells. We found no evidence of protection from SARS-CoV-2 through innate immunity or immunity induced by common β-coronaviruses. Cellular immune responses against SARS-CoV-2 were associated with time since exposure, suggesting that rapid cellular responses may contain SARS-CoV-2 infection below the thresholds required for a humoral response.
一些 SARS-CoV-2 暴露的个体在没有明显感染的情况下产生免疫。我们发现 11 名个体在长时间密切接触期间核酸检测均为阴性，且无感染的血清学诊断。由于这可能反映了自然免疫、先前冠状病毒暴露引起的交叉反应性免疫、新产生的免疫反应导致的流产感染，或者其他因素，我们的目标是确定这些个体对 SARS-CoV-2 的免疫情况。采集血液并分离出血浆和外周血单个核细胞（PBMC），用于检测针对 SARS-CoV-2 以及常见的β-冠状病毒 OC43 和 HKU1 的 IgG、IgA 和 IgM 抗体（Ab）。还测量了血浆中的受体阻断活性和干扰素-α（IFN-α）。对 SARS-CoV-2 的循环 T 细胞进行计数，并在体外刺激后区分 CD4 和 CD8 T 细胞反应。暴露但未感染的个体针对 SARS-CoV-2 刺突（S）呈血清阴性，而选择性地针对 OC43 核衣壳蛋白（N）呈反应性，这表明常见的β-冠状病毒暴露诱导了针对 SARS-CoV-2 N 的 Ab 交叉反应性。没有证据表明循环血管紧张素转换酶（ACE2）或 IFN-α可以提供保护。有 6 名个体对 SARS-CoV-2 有 T 细胞反应，其中 4 名涉及 CD4 和 CD8 T 细胞。我们没有发现通过固有免疫或常见的β-冠状病毒诱导的免疫对 SARS-CoV-2 有保护作用。针对 SARS-CoV-2 的细胞免疫反应与暴露时间有关，这表明快速的细胞反应可能在产生体液反应所需的阈值以下包含 SARS-CoV-2 感染。
