Hannover Medical School, Institute of Transplant Immunology, Hannover, Germany.
BREATH Site, German Center for Lung Research (DZL), Hannover, Germany.
Front Immunol. 2023 Mar 22;14:1120010. doi: 10.3389/fimmu.2023.1120010. eCollection 2023.
SARS-CoV-2 vaccination is the leading strategy to prevent severe courses after SARS-CoV-2 infection. In our study, we analyzed humoral and cellular immune responses in detail to three consecutive homologous or heterologous SARS-CoV-2 vaccinations and breakthrough infections.
Peripheral blood samples of n=20 individuals were analyzed in the time course of three SARS-CoV-2 vaccinations and/or breakthrough infection. S1-, RBD-, S2- and N-specific IgG antibodies were quantified using Luminex-based multiplex assays and electrochemiluminescence multiplex assays for surrogate neutralization in plasma. Changes in cellular immune components were determined via flow cytometry of whole blood samples.
All individuals (n=20) responded to vaccination with increasing S1-/RBD-/S2-specific IgG levels, whereas specific plasma IgA displayed individual variability. The third dose increased antibody inhibitory capacity (AIC) against immune-escape variants Beta and Omicron BA.1 independently of age. The mRNA-primed vaccination induced IgG and IgA immunity more efficiently, whereas vector-primed individuals displayed higher levels of memory T and B cells. Vaccinees showed SARS-CoV-2-specific T cell responses, which were further improved and specified after Omicron breakthrough infections in parallel to the appearance of new variant-specific antibodies.
In conclusion, the third vaccination was essential to increase IgG levels, mandatory to boost AIC against immune-escape variants, and induced SARS-CoV-2-specific T cells. Breakthrough infection with Omicron generates additional spike specificities covering all known variants.
SARS-CoV-2 疫苗接种是预防 SARS-CoV-2 感染后严重病程的主要策略。在我们的研究中,我们详细分析了连续三次同源或异源 SARS-CoV-2 疫苗接种和突破性感染后的体液和细胞免疫反应。
分析了 n=20 名个体在三次 SARS-CoV-2 疫苗接种和/或突破性感染过程中的外周血样本。使用基于 Luminex 的多重分析和用于替代中和的电化学发光多重分析来定量 S1-、RBD-、S2-和 N-特异性 IgG 抗体。通过全血样本的流式细胞术确定细胞免疫成分的变化。
所有个体(n=20)均对疫苗接种产生应答,S1-/RBD-/S2-特异性 IgG 水平升高,而特异性血浆 IgA 显示个体差异。第三剂独立于年龄增加了针对免疫逃逸变体 Beta 和 Omicron BA.1 的抗体抑制能力(AIC)。mRNA 疫苗诱导 IgG 和 IgA 免疫更有效,而载体疫苗诱导的记忆 T 和 B 细胞水平更高。接种疫苗者表现出 SARS-CoV-2 特异性 T 细胞反应,这些反应在 Omicron 突破性感染后进一步改善和特化,同时出现新的变体特异性抗体。
总之,第三次接种对于提高 IgG 水平至关重要,对于提高针对免疫逃逸变体的 AIC 是必需的,并且诱导了 SARS-CoV-2 特异性 T 细胞。Omicron 突破性感染产生了额外的刺突特异性,涵盖了所有已知变体。