Center for Virology, Medical University of Vienna, Vienna, Austria.
Center for Public Health, Medical University of Vienna, Vienna, Austria.
Front Immunol. 2022 Jul 19;13:946318. doi: 10.3389/fimmu.2022.946318. eCollection 2022.
The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Omicron (B.1.1.529) variant is the antigenically most distinct variant to date. As the heavily mutated spike protein enables neutralization escape, we studied serum-neutralizing activities of naïve and vaccinated individuals after Omicron BA.1 or BA.2 sub-lineage infections in live virus neutralization tests with Omicron BA.1, Omicron BA.2, wildtype (WT, B1.1), and Delta (B.1.617.2) strains. Serum samples obtained after WT infections and three-dose mRNA vaccinations with and without prior infection were included as controls.
Primary BA.1 infections yielded reduced neutralizing antibody levels against WT, Delta, and Omicron BA.2, while samples from BA.2-infected individuals showed almost no cross-neutralization against the other variants. Serum neutralization of Omicron BA.1 and BA.2 variants was detectable after three-dose mRNA vaccinations, but with reduced titers. Vaccination-breakthrough infections with either Omicron BA.1 or BA.2, however, generated equal cross-neutralizing antibody levels against all SARS-CoV-2 variants tested.
Our study demonstrates that although Omicron variants are able to enhance cross-neutralizing antibody levels in pre-immune individuals, primary infections with BA.1 or BA.2 induced mostly variant-specific neutralizing antibodies, emphasizing the differently shaped humoral immunity induced by the two Omicron variants. These data thus contribute substantially to the understanding of antibody responses induced by primary Omicron infections or multiple exposures to different SARS-CoV-2 variants and are of particular importance for developing vaccination strategies in the light of future emerging variants.
SARS-CoV-2（严重急性呼吸系统综合征冠状病毒 2）的奥密克戎（B.1.1.529）变异株是迄今为止抗原性差异最大的变异株。由于高度突变的刺突蛋白使其能够逃避中和作用，因此我们在活病毒中和试验中研究了奥密克戎 BA.1 或 BA.2 亚系感染后，未感染和接种疫苗的个体对奥密克戎 BA.1、BA.2、野生型（WT，B1.1）和德尔塔（B.1.617.2）株的血清中和活性。包括 WT 感染后和接种三剂 mRNA 疫苗（有无先前感染）获得的血清样本作为对照。
初次 BA.1 感染导致针对 WT、德尔塔和奥密克戎 BA.2 的中和抗体水平降低，而 BA.2 感染个体的样本对其他变体几乎没有交叉中和作用。接种三剂 mRNA 疫苗后可检测到对奥密克戎 BA.1 和 BA.2 变体的血清中和作用，但滴度降低。然而，奥密克戎 BA.1 或 BA.2 的突破性感染产生了针对所有测试 SARS-CoV-2 变体的同等交叉中和抗体水平。
我们的研究表明，尽管奥密克戎变体能够增强未免疫个体的交叉中和抗体水平，但 BA.1 或 BA.2 的初次感染主要诱导了变体特异性中和抗体，强调了两种奥密克戎变体诱导的不同形状的体液免疫。因此，这些数据对于理解针对奥密克戎初次感染或多次接触不同 SARS-CoV-2 变体的抗体反应具有重要意义，并且对于根据未来出现的变体制定疫苗接种策略尤为重要。
