Department of Virology, Paul-Ehrlich-Institute, Langen, Germany.
Institute of Clinical Pharmacology, University Hospital of RWTH, Aachen, Germany.
Allergy. 2022 Jul;77(7):2080-2089. doi: 10.1111/all.15189. Epub 2021 Dec 2.
The mRNA vaccine BNT162b2 (Comirnaty, BioNTech/Pfizer) and the vaccine candidate CVnCoV (Curevac) each encode a stabilized spike protein of SARS-CoV2 as antigen but differ with respect to the nature of the mRNA (modified versus unmodified nucleotides) and the mRNA amount (30 μg versus 12 μg RNA). This study characterizes antisera elicited by these two vaccines in comparison to convalescent sera.
Sera from BNT162b2 vaccinated healthcare workers, and sera from participants of a phase I trial vaccinated with 2, 4, 6, 8, or 12 μg CVnCoV and convalescent sera from hospitalized patients were analyzed by ELISA, neutralization tests, surface plasmon resonance (SPR), and peptide arrays.
BNT162b2-elicited sera and convalescent sera have a higher titer of spike-RBD-specific antibodies and neutralizing antibodies as compared to the CVnCoV-elicited sera. For all analyzed sera a reduction in binding and neutralizing antibodies was found for the lineage B.1.351 variant of concern. SPR analyses revealed that the CVnCoV-elicited sera have a lower fraction of slow-dissociating antibodies. Accordingly, the CVnCoV sera almost fail to compete with the spike-ACE2 interaction. The significance of common VOC mutations K417N, E484K, or N501Y focused on linear epitopes was analyzed using a peptide array approach. The peptide arrays showed a strong difference between convalescent sera and vaccine-elicited sera. Specifically, the linear epitope at position N501 was affected by the mutation and elucidates the escape of viral variants to antibodies against this linear epitope.
These data reveal differences in titer, neutralizing capacity, and affinity of the antibodies between BNT162b2- and CVnCoV-elicited sera, which could contribute to the apparent differences in vaccine efficacy.
mRNA 疫苗 BNT162b2（Comirnaty，辉瑞/BioNTech）和候选疫苗 CVnCoV（Curevac）均以 SARS-CoV2 的稳定刺突蛋白作为抗原，但在 mRNA 的性质（修饰核苷酸与未修饰核苷酸）和 mRNA 含量（30μg 与 12μg RNA）方面存在差异。本研究比较了这两种疫苗诱导的抗血清与恢复期血清。
分析了 BNT162b2 接种医护人员的血清，以及接种 2、4、6、8 或 12μg CVnCoV 的 I 期临床试验参与者的血清和住院患者的恢复期血清，采用 ELISA、中和试验、表面等离子体共振（SPR）和肽阵列进行分析。
与 CVnCoV 诱导的血清相比，BNT162b2 诱导的血清和恢复期血清的刺突-RBD 特异性抗体和中和抗体滴度更高。对于所有分析的血清，对关注的 B.1.351 谱系变体的结合和中和抗体均有降低。SPR 分析显示，CVnCoV 诱导的血清中具有较低比例的慢解离抗体。相应地，CVnCoV 血清几乎无法与刺突-ACE2 相互作用竞争。使用肽阵列方法分析了常见 VOC 突变 K417N、E484K 或 N501Y 对线性表位的意义。肽阵列显示恢复期血清和疫苗诱导的血清之间存在明显差异。具体而言，位置 N501 的线性表位受突变影响，并阐明了病毒变异体逃避针对该线性表位的抗体的情况。
这些数据揭示了 BNT162b2 和 CVnCoV 诱导的血清在滴度、中和能力和抗体亲和力方面的差异，这可能导致疫苗效力的明显差异。
