关键词: COVID-19 N protein S protein SARS-CoV-2 antibodies breakthrough immunity cellular immunity hybrid immunity vaccination

Mesh : Humans SARS-CoV-2 / immunology COVID-19 / immunology virology Immunity, Cellular Immunity, Humoral Antibodies, Viral / immunology blood Male Middle Aged Female Adult Spike Glycoprotein, Coronavirus / immunology Coronavirus Nucleocapsid Proteins / immunology COVID-19 Vaccines / immunology Immunoglobulin G / blood immunology Phosphoproteins / immunology CD8-Positive T-Lymphocytes / immunology Aged

来  源:   DOI:10.1134/S0006297924050080

Abstract:
The pandemic of a new coronavirus infection that has lasted for more than 3 years, is still accompanied by frequent mutations in the S protein of SARS-CoV-2 and emergence of new virus variants causing new disease outbreak. Of all coronaviral proteins, the S and N proteins are the most immunogenic. The aim of this study was to compare the features of the humoral and T-cell immune responses to the SARS-CoV-2 S and N proteins in people with different histories of interaction with this virus. The study included 27 individuals who had COVID-19 once, 23 people who were vaccinated twice with the Sputnik V vaccine and did not have COVID-19, 22 people who had COVID-19 and were vaccinated twice with Sputnik V 6-12 months after the disease, and 25 people who had COVID-19 twice. The level of antibodies was determined by the enzyme immunoassay, and the cellular immunity was assessed by the expression of CD107a on CD8high lymphocytes after recognition of SARS-CoV-2 antigens. It was shown that the humoral immune response to the N protein was formed mainly by short-lived plasma cells synthesizing IgG antibodies of all four subclasses with a gradual switch from IgG3 to IgG1. The response to the S protein was formed by short-lived plasma cells at the beginning of the response (IgG1 and IgG3 subclasses) and then by long-lived plasma cells (IgG1 subclass). The dynamics of antibody level synthesized by the short-lived plasma cells was described by the Fisher equation, while changes in the level of antibodies synthesized by the long-lived plasma cells were described by the Erlang equation. The level of antibodies in the groups with the hybrid immunity exceeded that in the group with the post-vaccination immunity; the highest antibody content was observed in the group with the breakthrough immunity. The cellular immunity to the S and N proteins differed depending on the mode of immune response induction (vaccination or disease). Importantly, the response of heterologous CD8+ T cell to the N proteins of other coronaviruses may be involved in the immune defense against SARS-CoV-2.
摘要:
持续了3年多的新型冠状病毒感染的大流行,仍然伴随着SARS-CoV-2的S蛋白的频繁突变以及引起新疾病爆发的新病毒变体的出现。在所有的冠状病毒蛋白中,S和N蛋白的免疫原性最强。这项研究的目的是比较与SARS-CoV-2S和N蛋白具有不同相互作用史的人的体液和T细胞免疫反应的特征。这项研究包括27名曾经感染过COVID-19的人,23人接种了两次人造卫星V疫苗,但没有接种COVID-19,22人接种了COVID-19,并在疾病发生6-12个月后接种了两次人造卫星V,25人两次感染COVID-19。通过酶免疫测定法测定抗体水平,通过识别SARS-CoV-2抗原后CD8high淋巴细胞上CD107a的表达来评估细胞免疫。研究表明,对N蛋白的体液免疫反应主要是由短寿命的浆细胞合成所有四个亚类的IgG抗体形成的,并从IgG3逐渐转换为IgG1。对S蛋白的反应由反应开始时的短寿命浆细胞(IgG1和IgG3亚类)形成,然后由长寿命浆细胞(IgG1亚类)形成。通过Fisher方程描述了由短寿命浆细胞合成的抗体水平的动力学,而由长寿命浆细胞合成的抗体水平的变化由Erlang方程描述。混合免疫组的抗体水平超过接种后免疫组的抗体水平;在具有突破免疫的组中观察到最高的抗体含量。对S和N蛋白的细胞免疫根据免疫应答诱导模式(疫苗接种或疾病)而不同。重要的是,异源CD8T细胞对其他冠状病毒N蛋白的反应可能参与了对SARS-CoV-2的免疫防御。
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