DataSheet_2_Booster dose of mRNA vaccine augments waning T cell and antibody responses against SARS-CoV-2.docx

A gradual decay in humoral and cellular immune responses over time upon SAR1S-CoV-2 vaccination may cause a lack of protective immunity. We conducted a longitudinal analysis of antibodies, T cells, and monocytes in 25 participants vaccinated with mRNA or ChAdOx1-S up to 12 weeks after the 3rd (booster) dose with mRNA vaccine. We observed a substantial increase in antibodies and CD8 T cells specific for the spike protein of SARS-CoV-2 after vaccination. Moreover, vaccination induced activated T cells expressing CD69, CD137 and producing IFN-γ and TNF-α. Virus-specific CD8 T cells showed predominantly memory phenotype. Although the level of antibodies and frequency of virus-specific T cells reduced 4-6 months after the 2nd dose, they were augmented after the 3rd dose followed by a decrease later. Importantly, T cells generated after the 3rd vaccination were also reactive against Omicron variant, indicated by a similar level of IFN-γ production after stimulation with Omicron peptides. Breakthrough infection in participants vaccinated with two doses induced more SARS-CoV-2-specific T cells than the booster vaccination. We found an upregulation of PD-L1 expression on monocytes but no accumulation of myeloid cells with MDSC-like immunosuppressive phenotype after the vaccination. Our results indicate that the 3rd vaccination fosters antibody and T cell immune response independently from vaccine type used for the first two injections. However, such immune response is attenuated over time, suggesting thereby the need for further vaccinations.

接种严重急性呼吸综合征冠状病毒2（SARS-CoV-2）疫苗后，体液与细胞免疫应答随时间逐渐衰减，可能导致保护性免疫缺失。本研究对25名受试者进行了纵向分析：这些受试者此前已接种mRNA或ChAdOx1-S疫苗，本研究对其在第3剂mRNA疫苗（mRNA vaccine）加强针接种后12周内的抗体、T细胞及单核细胞水平进行了检测。我们观察到，接种疫苗后，针对SARS-CoV-2刺突蛋白的抗体及CD8阳性T细胞水平显著升高。此外，疫苗接种可诱导表达CD69、CD137并分泌干扰素γ（IFN-γ）及肿瘤坏死因子α（TNF-α）的活化T细胞。病毒特异性CD8阳性T细胞主要表现为记忆表型。尽管第2剂接种后4~6个月，抗体水平及病毒特异性T细胞频率有所下降，但第3剂接种后二者均出现升高，随后再次降低。值得注意的是，第3剂疫苗接种后诱导产生的T细胞同样可对奥密克戎变异株产生免疫反应，奥密克戎肽段刺激后其干扰素γ的分泌水平与针对原型毒株的分泌水平相近，即可证实这一点。仅接种2剂疫苗的受试者发生突破性感染后，其体内SARS-CoV-2特异性T细胞水平较接受加强针接种的受试者更高。我们还发现，疫苗接种后单核细胞上程序性死亡受体配体1（PD-L1）的表达上调，但未出现具有髓系来源抑制性细胞（MDSC）样免疫抑制表型的髓系细胞蓄积。本研究结果表明，第3剂疫苗接种可强化抗体与T细胞免疫应答，且不受前两剂接种所用疫苗类型的影响。但此类免疫应答随时间推移会逐渐减弱，这提示后续仍需进行加强免疫接种。