Development of an Inactivated Vaccine against SARS CoV-2.

The rapid spread of SARS-CoV-2 with its mutating strains has posed a global threat to safety during this COVID-19 pandemic. Thus far, there are 123 candidate vaccines in human clinical trials and more than 190 candidates in preclinical development worldwide as per the WHO on 1 October 2021. The various types of vaccines that are currently approved for emergency use include viral vectors (e.g., adenovirus, University of Oxford/AstraZeneca, Gamaleya Sputnik V, and Johnson & Johnson), mRNA (Moderna and Pfizer-BioNTech), and whole inactivated (Sinovac Biotech and Sinopharm) vaccines. Amidst the emerging cases and shortages of vaccines for global distribution, it is vital to develop a vaccine candidate that recapitulates the severe and fatal progression of COVID-19 and further helps to cope with the current outbreak. Hence, we present the preclinical immunogenicity, protective efficacy, and safety evaluation of a whole-virion inactivated SARS-CoV-2 vaccine candidate (ERUCoV-VAC) formulated in aluminium hydroxide, in three animal models, BALB/c mice, transgenic mice (K18-hACE2), and ferrets. The hCoV-19/Turkey/ERAGEM-001/2020 strain was used for the safety evaluation of ERUCoV-VAC. It was found that ERUCoV-VAC was highly immunogenic and elicited a strong immune response in BALB/c mice. The protective efficacy of the vaccine in K18-hACE2 showed that ERUCoV-VAC induced complete protection of the mice from a lethal SARS-CoV-2 challenge. Similar viral clearance rates with the safety evaluation of the vaccine in upper respiratory tracts were also positively appreciable in the ferret models. ERUCoV-VAC has been authorized by the Turkish Medicines and Medical Devices Agency and has now entered phase 3 clinical development (NCT04942405). The name of ERUCoV-VAC has been changed to TURKOVAC in the phase 3 clinical trial.

The effects of genistein supplementation on fructose induced insulin resistance, oxidative stress and inflammation.

AIMS: This experimental study was designed to investigate the effects of 10weeks genistein administration on oxidative stress and inflammation in serum and liver of rats fed with fructose. MAIN METHODS: 6-8weeks old, 40 male Sprague-Dawley rats were included. Group 1 (control) was fed with standard chow food and 100µl/kg/day/rat dimethyl sulfoxide (DMSO) administered subcutaneously; group 2 (genistein) with standard chow food and 0.25mg/kg/day/rat genistein; group 3 (fructose) with standard chow food and drinking water 20% fructose, group 4 (fructose+genistein) with standard chow food, drinking water with 20% fructose and 0.25mg/kg/day/rat genistein. TNF-α, IL-6, visfatin as inflammatory markers and 8-isoprostane as a oxidative stress marker were measured by ELISA, glucose, triglyceride, total cholesterol, LDL-cholesterol and HDL-cholesterol by enzymatic colorimetric method, AST and ALT by kinetic UV method. KEY FINDINGS: Significantly high 8-isoprostane levels in serum (p<0.001) and liver (p<0.05) in group 3 compared to control group indicate that presence of oxidative stress. Significantly high TNF-α and IL-6 levels in serum (p<0.05) and liver (p<0.01) and visfatin levels in serum (p<0.001) of group 3 indicate inflammation accompanying insulin resistance and oxidative stress. Genistein administration to fructose group causes a significant decrease in HOMA-IR (p<0.001) and LDLC (p<0.05) level. Significantly lower serum 8-isoprostane (p<0.01) level indicates the antioxidant effect of genistein and significantly lower liver TNF-α (p<0.01), serum, liver IL-6(p<0.01) and serum visfatin (p<0.01) levels reflect the antiinflammatory effects of genistein. SIGNIFICANCE: Genistein administration to rats fed with fructose causes an ameliorating effect on HOMA-IR values and lipid status markers in addition to its antioxidant and antiinflammatory effects.

In vivo tissue-engineered allogenic trachea transplantation in rabbits: a preliminary report.

Conventional tracheal reconstruction techniques are not successful at restoring functional units in situations with extensive damage involving more than half the length of the trachea. For the first time, we investigated in vivo tissue-engineered trachea regeneration from a decellularized cadaveric trachea matrix with seeded adult adipose tissue-derived mesenchymal stem cells (MSCs) and investigated the integration of the matrix into the recipient tracheal side. For the procedure, 1.8-cm grafts were prepared from 3.5-cm tracheas of three donor rabbits. Then, tracheal grafts were rendered nonimmunogenic using a decellularization technique. MSCs isolated from recipient rabbit adipose tissue were cultured and marked before being seeded in the decellularized matrix. A total of 1.8 cm of the recipient tracheas was replaced with either a decellularized tracheal matrix (group 1) or tracheal matrix-seeded MSCs (group 2). Rabbits survived 17 ± 2 days in the first group, and the causes of death were separation in the anastomosis region, airway obstruction, and infection. In the second group, animals were sacrificed on the 30th, 60th, and 90th days of follow-up. Histopathological analysis revealed the integration of MSCs seeded-decellularized cadaveric tracheas to the recipient tracheal sides and increased angiogenesis. The MSCs were traced by fluorescence microscopy in the ciliated epithelium, under the epithelium, and in the cartilage of the integrated new trachea. Tracheas generated by autologous cells and tissue-engineering techniques will be a great source for the treatment of life-threatening tracheal injuries after the completion of related studies.