Aerosolized Ad5-nCoV booster vaccination elicited potent immune response against the SARS-CoV-2 Omicron variant after inactivated COVID-19 vaccine priming

The SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant around the world and exhibits immune escape to current COVID-19 vaccines to some extent due to its numerous spike mutations. Here, we evaluated the immune responses to booster vaccination with intramuscular adenovirus-vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines 6 months prior. We found that the Ad5-nCoV booster induced potent neutralizing activity against the wild-type virus and Omicron variant, while aerosolized Ad5-nCoV generated the greatest neutralizing antibody responses against the Omicron variant at day 28 after booster vaccination, at 14.1-fold that of CoronaVac, 5.6-fold that of ZF2001 and 2.0-fold that of intramuscular Ad5-nCoV. Similarly, the aerosolized Ad5-nCoV booster produced the greatest IFN{gamma} T-cell response at day 14 after booster vaccination. The IFN{gamma} T-cell response to aerosolized Ad5-nCoV was 12.8-fold for CoronaVac, 16.5-fold for ZF2001, and 5.0-fold for intramuscular Ad5-nCoV. Aerosolized Ad5-nCoV booster also produced the greatest spike-specific B cell response. Our findings suggest that inactivated vaccine recipients should consider adenovirus-vectored vaccine boosters in China and that aerosolized Ad5-nCoV may provide a more efficient alternative in response to the spread of the Omicron variant.

Impact of various vaccine boosters on neutralization against Omicron following prime vaccinations with inactivated or adenovirus-vectored vaccine

Since the first report on November 24, 2021, the Omicron SARS-CoV-2 variant is now overwhelmingly spreading across the world. Two SARS-CoV-2 inactivated vaccines (IAVs), one recombinant protein subunit vaccine (PRV), and one adenovirus-vectored vaccine (AdV) have been widely administrated in many countries including China to pursue herd immunity. Here we investigated cross-neutralizing activities in 341 human serum specimens elicited by full-course vaccinations with IAV, PRV and AdV, and by various vaccine boosters following prime IAV and AdV vaccinations. We found that all types of vaccines induced significantly lower neutralizing antibody titers against the Omicron variant than against the prototype strain. For prime vaccinations with IAV and AdV, heterologous boosters with AdV and PRV, respectively, elevated serum Omicron-neutralizing activities to the highest degrees. In a mouse model, we further demonstrated that among a series of variant-derived RBD-encoding mRNA vaccine boosters, it is only the Omicron booster that significantly enhanced Omicron neutralizing antibody titers compared with the prototype booster following a prime immunization with a prototype S-encoding mRNA vaccine candidate. In summary, our systematical investigations of various vaccine boosters inform potential booster administrations in the future to combat the Omicron variant.

Influence of P27RF-RhO mRNA gene silencing in drug sensitivity of 5-fluorouracil in liver cancer SMMC7721 cell line / 吉林大学学报(医学版)

Objective:To investigate the influence of P27RF-Rho mRNA gene silencing in the drug sensitivity of 5-fluorouracil(5-Fu)to the liver cancer SMMC cell line,and to provide theoretical basis for the treatment of advanced liver cancer.Methods:The P27RF-Rho RNAi vector was constructed and the P27RF-Rho gene silencing lentivirus were used to infect the SMMC7721 cells.Western blotting method was used to detect the gene silencing effect.The SMMC7721 cells were divided into Scramble-siRNA group, 5-Fu group, P27RF-Rho siRNA group and P27RF-Rho siRNA + 5-Fu group.Western blotting was used to detect the transfection efficiency of RNAi.MTT method was used to detect the cell growth in various groups.Scratching test was used to detect the migration ability of cells in various groups.Transwell experiment were used to detect the invasion ability of cells in various groups.The expressions of P27 and RhoC protein were detected by Western blotting method.Results:P27RF-Rho RNAi lentiviral vector was successfully constructed.The Western blotting results showed that the expression of P27RF-Rho protein in P27RF-Rho siRNA group was decreased compared with 5-Fu group and Scramble-siRNA group(P<0.05).Compared with other three groups, the growth speed of the cells in P27RF-Rho siRNA + 5-Fu group was significantly decreased(P<0.05).The migration ability of the cells in P27RF-Rho siRNA + 5-Fu group was significantly lower than those in other three groups (P<0.01);the average number of cells passing through the Transwell microporous membrane was significantly less than those in other three groups (P<0.01).The Western blotting analysis results showed that the expression level of P27 protein in the cells in P27RF-Rho siRNA + 5-Fu group was significantly higher than those in other three groups(P<0.05);the expression level of RhoC protein was significantly lower than those in other three groups(P<0.05).Conclusion:P27RF-Rho gene silencing can significantly enhance the drug sensitivity of 5-Fu to SMMC7721 cells.

Protective effect of amlodipine against contrast agent-induced renal injury in elderly patients with coronary heart disease / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the protective effect of amlodipine against contrast agent-induced renal injury in elderly patients with coronary heart disease.</p><p><b>METHODS</b>A total of 189 elderly patients (>60 years) with coronary heart disease undergoing coronary artery angiography were randomly assigned into amlodipine group and control group to receive amlodipine or placebo, respectively, before and after administration of the contrast agent. At 24 h, 48 h and 5 days after contrast agent administration, the parameters of renal function were measured including serum cystatin C, urea nitrogen, creatinine, creatinine clearance rate, urine β2-microglobulin, and urine N-acetyl-β-glucosaminidase.</p><p><b>RESULTS</b>In both groups, the contrast agents obviously affected the renal functions of the patients (P<0.05). At 24 h after contrast administration, the levels of serum cystatin C, urine β2-microglobulin and urine NAG were significantly lower in amlodipine group than in the control group, but the other functional parameters showed no significant difference. At 48 h after contrast administration, the glomerular and tubular functional parameters were all superior in amlodipine group (P<0.05). At 5 days, the two groups showed significant differences in such glomerular and tubular functional parameters as urea nitrogen, creatinine, creatinine clearance rate, urine β2-microglobulin, and urine NAG (P<0.05), but not in serum cystatin C level. The incidence of contrast agent-induced nephropathy was significantly lower in amlodipine group than in the control group (5/95 vs 10/94, P<0.05).</p><p><b>CONCLUSIONS</b>Amlodipine offers protection against radiographic contrast agent-induced renal injury in elderly patients with coronary heart disease.</p>

Graft injury and expression of redox factor-1 during early period after liver transplantation in rats / 中华普通外科杂志

Objective To study the relationship between graft injury and expression of redox factor-1 in early period after liver transplantation in rats. Methods One hundred and fifty adult male Wistar rats were randomly divided into three groups: liver transplant group, sham surgery group and control group. Animals were sacrificed in each group at different time points: 3,6,9, 12,24 hour after liver transplantation. The changes and significance of the expression of Ref-1 were explored by immunohistochemistry, serology and histopathology. Results Compared with sham surgery group and control group, the expression of Ref-1 protein in transplant group was higher than that in other two groups in early period after liver transplantation ( P ＜ 0. 05 ). In pathology there were lots of inflammation cells infiltration around the portal veins, and cell damage of hepatic tissue, while that in sham surgery and control group was comparatively slight. Serum ALT and AST values reached the peak at 6 ～ 12 h, and decreaced significantly after 12 h ( P ＜ 0. 05 ). Conclusions Graft injury after liver transplantation during early period reaches peak at 6 hour and then decreased. Hepatic ischemic reperfusion injury promotes Ref-1 expression, which in turn compensates for programme cell death induced by the injury.