Emerging SARS-CoV-2 variants reduce neutralization sensitivity to convalescent sera and monoclonal antibodies

Coronaviruses are enveloped,positive-stranded RNA viruses that contain the largest known RNA genomes to date.As severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continues to circulate in the human population,multiple mutations have accumulated over time,which may affect its transmission,virulence and antigenicity.

Reduced neutralization of SARS-CoV-2 B.1.617 variant by convalescent and vaccinated sera

Coronavirus disease 2019(COVID-19)is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The Spike protein that mediates coronavirus entry into host cells is a major target for COVID-19 vaccines and antibody therapeutics.However,multiple variants of SARS-CoV-2 have emerged,which may potentially compromise vaccine effectiveness.Using a pseudovirus-based assay,we evaluated SARS-CoV-2 cell entry mediated by the viral Spike B.1.617 and B.1.1.7 variants.We also compared the neutralization ability of monoclonal antibodies from convalescent sera and neutralizing antibodies(NAbs)elicited by CoronaVac(inactivated vaccine)and ZF2001(RBD-subunit vaccine)against B.1.617 and B.1.1.7 variants.Our results showed that,compared to D614G and B.1.1.7 variants,B.1.617 shows enhanced viral entry and membrane fusion,as well as more resistant to antibody neutralization.These findings have important implications for understanding viral infectivity and for immunization policy against SARS-CoV-2 variants.

Augmenter of Liver Regeneration Monoclonal Antibody Promotes Apoptosis of Hepatocellular Carcinoma Cells

Background and Aims: Hepatocellular carcinoma (HCC) is one of the most common types of cancer, often resulting in death. Augmenter of liver regeneration (ALR), a widely expressed multifunctional protein, has roles in liver dis-ease. In our previous study, we reported that ALR knock-down inhibited cell proliferation and promoted cell death. However, there is no study on the roles of ALR in HCC. Methods: We used in vitro and in vivo models to inves-tigate the effects of ALR in HCC as well as its mechanism of action. We produced and characterized a human ALR-specific monoclonal antibody (mAb) and investigated the effects of the mAb in HCC cells. Results: The purified ALR-specific mAb matched the predicted molecular weight of IgG heavy and light chains. Thereafter, we used the ALR-specific mAb as a therapeutic strategy to suppress tumor growth in nude mice. Additionally, we assessed the prolif-eration and viability of three HCC cell lines, Hep G2, Huh-7, and MHC97-H, treated with the ALR-specific mAb. Com-pared with controls, tumor growth was inhibited in mice treated with the ALR-specific mAb at 5 mg/kg, as shown by hematoxylin and eosin staining and terminal deoxynu-cleotidyl transferase dUTP nick end labeling. Simultaneous treatment with the ALR-specific mAb and adriamycin pro-moted apoptosis, whereas treatment with the ALR-specific mAb alone inhibited cell proliferation. Conclusions: The ALR-specific mAb might be a novel therapy for HCC by blocking extracellular ALR.