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.