DataSheet_1_In-depth analysis of T cell immunity and antibody responses in heterologous prime-boost-boost vaccine regimens against SARS-CoV-2 and Omicron variant.pdf

With the emergence of novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Variants of Concern (VOCs), vaccination studies that elucidate the efficiency and effectiveness of a vaccination campaign are critical to assess the durability and the protective immunity provided by vaccines. SARS-CoV-2 vaccines have been found to induce robust humoral and cell-mediated immunity in individuals vaccinated with homologous vaccination regimens. Recent studies also suggest improved immune response against SARS-CoV-2 when heterologous vaccination strategies are employed. Yet, few data exist on the extent to which heterologous prime-boost-boost vaccinations with two different vaccine platforms have an impact on the T cell-mediated immune responses with a special emphasis on the currently dominantly circulating Omicron strain. In this study, we collected serum and peripheral blood mononuclear cells (PBMCs) from 57 study participants of median 35-year old’s working in the health care field, who have received different vaccination regimens. Neutralization assays revealed robust but decreased neutralization of Omicron VOC, including BA.1 and BA.4/5, compared to WT SARS-CoV-2 in all vaccine groups and increased WT SARS-CoV-2 binding and neutralizing antibodies titers in homologous mRNA prime-boost-boost study participants. By investigating cytokine production, we found that homologous and heterologous prime-boost-boost-vaccination induces a robust cytokine response of CD4+ and CD8+ T cells. Collectively, our results indicate robust humoral and T cell mediated immunity against Omicron in homologous and heterologous prime-boost-boost vaccinated study participants, which might serve as a guide for policy decisions.

随着新型严重急性呼吸综合征冠状病毒2型（Severe Acute Respiratory Syndrome Coronavirus-2, SARS-CoV-2）关切变异株（Variants of Concern, VOCs）的出现，阐明疫苗接种运动效率与有效性的相关研究，对于评估疫苗所诱导的持久性保护性免疫力至关重要。现有研究表明，采用同源接种方案的疫苗接种者体内可诱导强烈的体液免疫与细胞介导免疫；近期研究还提示，采用异源接种策略可改善针对SARS-CoV-2的免疫应答。然而，针对使用两种不同疫苗平台的异源初免-加强-加强（prime-boost-boost）接种方案，其对T细胞介导免疫应答的影响，尤其是针对当前主流流行的奥密克戎（Omicron）毒株的相关数据仍较为有限。本研究从57名中位年龄为35岁的医疗工作者研究对象中采集了血清与外周血单个核细胞（peripheral blood mononuclear cells, PBMCs），这些对象均接受了不同的疫苗接种方案。中和试验结果显示，相较于野生型（Wild Type, WT）SARS-CoV-2，所有疫苗组对包含BA.1与BA.4/5在内的奥密克戎关切变异株的中和活性虽仍较强但有所下降；而同源mRNA初免-加强-加强接种的研究对象体内，针对野生型SARS-CoV-2的结合抗体与中和抗体滴度均有所升高。通过检测细胞因子产生情况，本研究发现同源与异源初免-加强-加强接种均可诱导CD4+与CD8+ T细胞产生强烈的细胞因子应答。综上，本研究结果表明，接受同源或异源初免-加强-加强接种的研究对象体内，针对奥密克戎毒株的体液免疫与T细胞介导免疫均表现强劲，该结果可为相关政策制定提供参考依据。