In response to the COVID-19 pandemic, multiple vaccines were developed using platforms such as viral vectors and mRNA technology. Here, we report humoral and cellular immunogenicity data from human phase 1 clinical trials investigating two recombinant Modified Vaccinia virus Ankara vaccine candidates, MVA-SARS-2-S and MVA-SARS-2-ST, encoding the native and the prefusion-stabilized SARS-CoV-2 spike protein, respectively. MVA-SARS-2-ST was more immunogenic than MVA-SARS-2-S, but both were less immunogenic compared to licensed mRNA- and ChAd-based vaccines in SARS-CoV-2 naïve individuals. In heterologous vaccination, previous MVA-SARS-2-S vaccination enhanced T cell functionality and MVA-SARS-2-ST boosted the frequency of T cells and S1-specific IgG levels when used as a third vaccination. While the vaccine candidate containing the prefusion-stabilized spike elicited predominantly S1-specific responses, immunity to the candidate with the native spike was skewed towards S2-specific responses. These data demonstrate how the spike antigen conformation, using the same viral vector, directly affects vaccine immunogenicity in humans.

为了应对 COVID-19 大流行，利用病毒载体和 mRNA 技术等平台开发了多种疫苗。在此，我们报告了人体 1 期临床试验的体液和细胞免疫原性数据，该试验研究了两种重组改良牛痘病毒安卡拉候选疫苗 MVA-SARS-2-S 和 MVA-SARS-2-ST，编码天然和预输注稳定的 SARS分别为-CoV-2刺突蛋白。MVA-SARS-2-ST 比 MVA-SARS-2-S 具有更高的免疫原性，但与 SARS-CoV-2 初次接触者中许可的基于 mRNA 和 ChAd 的疫苗相比，两者的免疫原性较低。在异源疫苗接种中，先前的 MVA-SARS-2-S 疫苗接种增强了 T 细胞功能，而当用作第三次疫苗接种时，MVA-SARS-2-ST 提高了 T 细胞的频率和 S1 特异性 IgG 水平。虽然含有预融合稳定刺突的候选疫苗主要引起 S1 特异性反应，但对具有天然刺突的候选疫苗的免疫力偏向于 S2 特异性反应。这些数据证明了使用相同病毒载体的刺突抗原构象如何直接影响人类疫苗的免疫原性。