Two-adjuvant multiantigen candidate vaccine induces superior protective immune responses against SARS-CoV-2 challenge. Sun et al

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), this virus has spread worldwide, causing the ongoing coronavirus disease 2019 (COVID-19) pandemic, which has resulted in over two million deaths (https://covid.cdc.gov/covid-data-tracker/#global-counts-rates). Developing a vaccine that can not only prevent COVID-19 but also stop the transmission of SARS-CoV-2, especially with the ability to clear the virus in the upper respiratory tract (URT), is the major target of vaccine developers. In this study, we first tested the synergistic adjuvant effects of nonpathogenic Escherichia coli-derived flagellin (KF) and cGAMP in vivo and in vitro by using bone marrow-derived dendritic cells (BMDCs) and the model antigen ovalbumin (OVA). Subsequently, we evaluated the optimal forms of the S protein for use as an antigen. Finally, we prepared a multiantigen-based SARS-CoV-2 vaccine formulated with this combined adjuvant and then compared its immunogenicity and protective efficacy with those of a reference inactivated vaccine in mouse models. We aimed to search for a candidate vaccine that has the potential to elicit humoral, cellular, and mucosal immunity to prevent viral infection and disease and to promote efficient viral clearance from the URT.

自严重急性呼吸综合征冠状病毒2（severe acute respiratory syndrome coronavirus 2，SARS-CoV-2）出现以来，该病毒已在全球范围内传播，引发了持续的2019冠状病毒病（Corona Virus Disease 2019，COVID-19）大流行，已造成超200万人死亡（数据来源：https://covid.cdc.gov/covid-data-tracker/#global-counts-rates）。研发一款不仅能够预防2019冠状病毒病，还能阻断SARS-CoV-2传播，尤其具备清除上呼吸道（upper respiratory tract，URT）内病毒能力的疫苗，是疫苗研发人员的核心目标。本研究首先利用骨髓来源树突状细胞（bone marrow-derived dendritic cells，BMDCs）与模式抗原卵清蛋白（ovalbumin，OVA），在体内及体外检测了非致病性大肠杆菌（Escherichia coli）来源的鞭毛蛋白（flagellin，KF）与环鸟苷酸-腺苷酸（cGAMP）的协同佐剂效应；随后评估了用作抗原的S蛋白（S protein）的最优形式；最终制备了搭载该复合佐剂的多抗原型SARS-CoV-2疫苗，并在小鼠模型中对比了其与参比灭活疫苗的免疫原性及保护效力。本研究旨在筛选出可诱导体液免疫、细胞免疫及黏膜免疫，以预防病毒感染与发病，并促进上呼吸道病毒高效清除的候选疫苗。