关键词: COVID-19 vaccination HCoV cross-reactive antibodies dynamics influenza memory B cell original antigenic sin plasmablast

Mesh : Humans Antibodies, Viral / blood immunology COVID-19 / immunology prevention & control Memory B Cells / immunology SARS-CoV-2 / immunology COVID-19 Vaccines / immunology Immunity, Humoral Male Adult Cross Reactions / immunology Female Plasma Cells / immunology Middle Aged Immunoglobulin G / immunology blood Vaccination Influenza Vaccines / immunology Immunologic Memory / immunology Antibodies, Neutralizing / immunology blood Epitopes, B-Lymphocyte / immunology B-Lymphocytes / immunology Spike Glycoprotein, Coronavirus / immunology Kinetics

来  源:   DOI:10.3389/fimmu.2024.1382911   PDF(Pubmed)

Abstract:
UNASSIGNED: COVID-19 vaccines are highly effective in inducing protective immunity. While the serum antibody response to COVID-19 vaccination has been studied in depth, our knowledge of the underlying plasmablast and memory B cell (Bmem) responses is still incomplete. Here, we determined the antibody and B cell response to COVID-19 vaccination in a naïve population and contrasted it with the response to a single influenza vaccination in a primed cohort. In addition, we analyzed the antibody and B cell responses against the four endemic human coronaviruses (HCoVs).
UNASSIGNED: Measurement of specific plasma IgG antibodies was combined with functional analyses of antibody-secreting plasmablasts and Bmems. SARS-CoV-2- and HCoV-specific IgG antibodies were quantified with an in-house bead-based multiplexed immunoassay.
UNASSIGNED: The antibody and B cell responses to COVID-19 vaccination reflected the kinetics of a prime-boost immunization, characterized by a slow and moderate primary response and a faster and stronger secondary response. In contrast, the influenza vaccinees possessed robust immune memory for the vaccine antigens prior to vaccination, and the recall vaccination moderately boosted antibody production and Bmem responses. Antibody levels and Bmem responses waned several months after the 2nd COVID-19 vaccination, but were restored upon the 3rd vaccination. The COVID-19 vaccine-induced antibodies mainly targeted novel, non-cross-reactive S1 epitopes of the viral spike protein, while cross-reactive S2 epitopes were less immunogenic. Booster vaccination not only strongly enhanced neutralizing antibodies against an original SARS-CoV-2 strain, but also induced neutralizing antibodies against the Omicron BA.2 variant. We observed a 100% plasma antibody prevalence against the S1 subunits of HCoVs, which was not affected by vaccination.
UNASSIGNED: Overall, by complementing classical serology with a functional evaluation of plasmablasts and memory B cells we provide new insights into the specificity of COVID-19 vaccine-induced antibody and B cell responses.
摘要:
COVID-19疫苗在诱导保护性免疫方面非常有效。虽然对COVID-19疫苗接种的血清抗体反应进行了深入研究,我们对潜在的浆细胞和记忆B细胞(Bmem)反应的了解仍然不完整。这里,我们测定了未接种人群对COVID-19疫苗的抗体和B细胞应答,并将其与引发队列中单一流感疫苗的应答进行了对比.此外,我们分析了针对四种地方性人冠状病毒(HCoV)的抗体和B细胞应答.
特异性血浆IgG抗体的测量与分泌抗体的成浆细胞和Bmems的功能分析相结合。SARS-CoV-2和HCoV特异性IgG抗体用内部基于珠子的多重免疫测定法定量。
对COVID-19疫苗接种的抗体和B细胞反应反映了初次加强免疫的动力学,以缓慢和中等的初级反应和更快和更强的次级反应为特征。相比之下,流感疫苗接种前对疫苗抗原具有强大的免疫记忆,召回疫苗适度地增强了抗体产生和Bmem反应。第二次COVID-19疫苗接种后几个月,抗体水平和Bmem反应减弱,但在第三次接种疫苗后恢复。COVID-19疫苗诱导的抗体主要靶向新型,病毒刺突蛋白的非交叉反应S1表位,而交叉反应的S2表位免疫原性较低。加强疫苗接种不仅强烈增强了针对原始SARS-CoV-2菌株的中和抗体,而且还诱导了针对OmicronBA.2变体的中和抗体。我们观察到针对HCoVS1亚基的100%血浆抗体患病率,不受疫苗接种的影响。
总的来说,通过对成浆细胞和记忆B细胞的功能评估来补充经典血清学,我们为COVID-19疫苗诱导的抗体和B细胞反应的特异性提供了新的见解。
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