Characterization of cross-reactive monoclonal antibodies against SARS-CoV-1 and SARS-CoV-2: Implication for rational design and development of pan-sarbecovirus vaccines and neutralizing antibodies.

Emergence of various circulating SARS-CoV-2 variants of concern (VOCs) promotes the identification of pan-sarbecovirus vaccines and broadly neutralizing antibodies (bNAbs). Here, to characterize monoclonal antibodies cross-reactive against both SARS-CoV-1 and SARS-CoV-2 and to search the criterion for bNAbs against all emerging SARS-CoV-2, we isolated several SARS-CoV-1-cross-reactive monoclonal antibodies (mAbs) from a wildtype SARS-CoV-2 convalescent donor. These antibodies showed broad binding capacity and cross-neutralizing potency against various SARS-CoV-2 VOCs, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta), but failed to efficiently neutralize Omicron variant and its sublineages. Structural analysis revealed how Omicron sublineages, but not other VOCs, efficiently evade an antibody family cross-reactive against SARS-CoV-1 through their escape mutations. Further evaluation of a series of SARS-CoV-1/2-cross-reactive bNAbs showed a negative correlation between the neutralizing activities against SARS-CoV-1 and SARS-CoV-2 Omicron variant. Together, these results suggest the necessity of using cross-neutralization against SARS-CoV-1 and SARS-CoV-2 Omicron as criteria for rational design and development of potent pan-sarbecovirus vaccines and bNAbs.

Anillin facilitates cell proliferation and induces tumor growth of hepatocellular carcinoma via miR-138/SOX4 axis regulation

Actin-binding protein Anillin plays a pivotal role in regulating cytokinesis during the cell cycle, and involves in tumorigenesis and progress. However, the exact regulation mechanism of Anillin in human hepatocellular carcinoma (HCC) remains largely unknown. In this study, we examined and verified the anomalous high expression of Anillin in both HCC patients'specimens and HCC cell lines. High expression of Anillin is associated with dismal clinicopathologic features of HCC patients and poor prognosis. We conducted loss-of and gain-of function studies in HCC Hep3B cells. Anillin presented a significantly facilitating effect on cell proliferation in vitro and induced remarkable tumor growth in vivo. We found that the over-expression of Anillin was driven by a potential axis of miR-138/SOX4. Transcription factor SOX4 presented a high expression profile positive correlated with Anillin, and ChIP assay validated the interaction between SOX4 and the specific sequence of the promoter region of Anillin gene. While, we verified miR-138 as an upstream regulator of SOX4, which is abrogated in HCC cells and exerts degenerating effect on SOX4 mRNA. In our conclusion, Anillin facilitates the cell proliferation and enhances tumor growth of HCC, and is modulated by miR-138/SOX4 axis which regulates the transcriptional activity of Anillin. Findings above demonstrate us a probable axis for HCC diagnosis and treatment. SUMMARY OF THE MAIN POINT: Anillin facilitates the cell proliferation and enhances tumor growth in HCC. The transcriptional activity of Anillin is modulated by miR-138/SOX4 axis. Findings above demonstrate us a probable axis for HCC diagnosis and treatment.