Grikscheit Katharina, Rabenau Holger F, Ghodratian Zahra, Widera Marek, Wilhelm Alexander, Toptan Grabmair Tuna, Hoehl Sebastian, Layer Emily, Helfritz Fabian, Ciesek Sandra
Institute for Medical Virology, University Hospital Frankfurt, Goethe University Frankfurt, 60596 Frankfurt, Germany.
Health Protection Authority of the City of Frankfurt am Main, 60313 Frankfurt am Main, Germany.
Vaccines (Basel). 2022 Jul 21;10(7):1163. doi: 10.3390/vaccines10071163.
The emergence of SARS-CoV-2 Omicron subvariants prompted countries to call for accelerated booster vaccinations to limit disease and transmission. Here, we characterized correlates of protection over time after the second booster or after Omicron BA.1 infection comparing variants of concern (VOCs). Sera from subjects before and two and seven weeks after the second booster or after Omicron infection were examined for the level of Spike receptor-binding-domain (RBD)-specific antibodies. Furthermore, neutralizing antibodies (nABs) were characterized in in vitro neutralization assays comparing the variants of concern Alpha, Beta, Delta, and Omicron BA.1 and BA.2 against the ancestral strain B.1. Here, the second booster resulted in an increase in anti-RBD-IgG-antibodies, remaining nearly constant over time, accompanied by an increase in nABs against B.1 and the VOCs Alpha, Beta, Delta, and Omicron BA.1 and BA.2. However, compared to B.1, the neutralizing capacity against the Omicron subvariants remained low and was limited after the second booster vaccination. This indicates that antibody-mediated protection against infection with this VOC is unlikely, as evidenced by the fact that three individuals of our study cohort became infected with Omicron BA.1 after the second booster. T cell activation was measured by interferon-gamma release assays in a subgroup of subjects and was increased in all subjects tested after the second booster vaccination, correlating with the amount of Spike-specific antibodies. In subjects with Omicron BA.1 breakthrough infection, a significant increase in nABs to all VOCs studied was observed independently of booster vaccinations. Taken together, our data indicate that a second booster or Omicron BA.1 infection mediate a substantial increase in anti-Spike IgG antibodies; however, infection with Omicron BA.1 induced a stronger increase in neutralizing antibodies against the different VOCs.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）奥密克戎亚变体的出现促使各国呼吁加速加强疫苗接种，以限制疾病传播。在此，我们比较了关注变体（VOCs），对第二次加强疫苗接种后或奥密克戎BA.1感染后的不同时间点的保护相关性进行了表征。检测了受试者在第二次加强疫苗接种前以及接种后两周和七周或奥密克戎感染后的血清中刺突蛋白受体结合域（RBD）特异性抗体的水平。此外，在体外中和试验中比较了关注变体阿尔法、贝塔、德尔塔以及奥密克戎BA.1和BA.2针对原始毒株B.1的中和抗体（nABs）。在此，第二次加强疫苗接种导致抗RBD-IgG抗体增加，且随时间基本保持恒定，同时针对B.1以及VOCs阿尔法、贝塔、德尔塔和奥密克戎BA.1和BA.2的nABs也有所增加。然而，与B.1相比，针对奥密克戎亚变体的中和能力仍然较低，且在第二次加强疫苗接种后有限。这表明抗体介导的针对该VOC感染的保护不太可能，我们研究队列中的三名个体在第二次加强疫苗接种后感染了奥密克戎BA.1就证明了这一点。在一个亚组受试者中通过干扰素-γ释放试验测量了T细胞活化情况，在第二次加强疫苗接种后所有检测的受试者中T细胞活化均增加，且与刺突特异性抗体的量相关。在发生奥密克戎BA.1突破性感染的受试者中，观察到针对所有研究的VOCs的nABs显著增加，与加强疫苗接种无关。综上所述，我们的数据表明，第二次加强疫苗接种或奥密克戎BA.1感染介导了抗刺突IgG抗体的大幅增加；然而，奥密克戎BA.1感染诱导针对不同VOCs的中和抗体有更强的增加。
