Safety pharmacology of human endogenous retrovirus-enveloped baculoviral DNA vaccines against SARS-CoV-2 in Sprague-Dawley rats and beagle dogs.

The coronavirus disease 2019 (COVID-19) emerged as a major global health crisis, posing significant health, economic, and social challenges. Vaccine development has been a crucial response to the severe-acute-respiratory-syndrome-related coronavirus-2 pandemic owing to the critical role of immunization in controlling infectious diseases, leading to the expedited development of several effective vaccines. Although mRNA platform-based COVID-19 vaccines authorized under emergency-use authorization have been administered globally, concerns regarding the vaccines have increased owing to the occurrence of various side effects. The present study aimed to evaluate the safety of a non-replicating recombinant baculovirus expressing the human endogenous retrovirus envelope gene (AcHERV) vaccine encoding SARS-CoV-2 antigens. Owing to the limited number of existing safety pharmacology studies on AcHERV as a viral vector vaccine, we conducted neurobehavior (Modified Irwin's Test), body temperature, and respiratory function studies in rats and cardiovascular system studies in male beagle dogs, which were administered the AcHERV-COVID-19 vaccine using telemetry. The safety assessment revealed no significant toxicological alterations. However, in rats, both sexes administered with the AcHERV-COVID-19 vaccine exhibited a temporary increase in body temperature, which normalized or showed signs of recovery. In conclusion, AcHERV-COVID-19 demonstrates a sufficient safety profile that supports its potential evaluation in future clinical trials.

[A case of pegylated interferon alpha-2a monotherapy in a peritoneal dialysis patient with chronic hepatitis C].

Pegylated interferon (PEG-IFN) is now the standard treatment for chronic hepatitis C. But, there are few reports about patients with end stage renal disease, and treatment protocol for HCV infection has not been determined, particularly in patients on peritoneal dialysis. We experienced a case of a peritoneal dialysis patient with chronic hepatitis C who was successfully treated with PEG-IFN monotherapy. A 50-year old man was undergoing peritoneal dialysis because of diabetic nephropathy. Considering that his HCV genotype was 2, we decided to treat him with PEG-IFN alpha-2a monotherapy 4 month after the beginning of peritoneal dialysis. We adopted a 90 mg of PEG-IFN administration. After the injection of PEG-IFN, dialysate concentration of PEG-IFN did not change significantly. HCV-RNA disappeared at the 4th week and sustatined virus response was achieved thereafter. No side effects were observed during the treatment of 24 weeks. PEG-IFN monotherapy with dose modification may be a safe and effective treatment for HCV infection in patients undergoing peritoneal dialysis.

Expression and functional characterization of the system L amino acid transporter in KB human oral epidermoid carcinoma cells.

We have examined the expression and function of system l amino acid transporter in KB human oral epidermoid carcinoma cells. The KB cells express l-type amino acid transporter 1 (LAT1) in plasma membrane, but not l-type amino acid transporter 2 (LAT2). The [14C]l-leucine uptake by KB cells is inhibited by system l selective inhibitor BCH. The majority of [14C]l-leucine uptake is, therefore, mediated by LAT1. These results suggest that the transport of neutral amino acids including several essential amino acids into the KB cells mediated by LAT1 and the specific inhibition of LAT1 in oral cancer cells will be a new rationale for anti-cancer therapy.