A Phase II/III, Multicenter, Observer-blinded, Randomized, Non-inferiority and Safety, study of typhoid conjugate vaccine (EuTCV) compared to Typbar-TCV® in healthy 6 Months-45 years aged participants.

The typhoid conjugate vaccine (TCV) ensures a long-lasting protective immune response, requires fewer doses and is fit for children under 2 years of age. From Phase I study, EuTCV displayed considerable immunogenicity and reliable safety, thus endorsing further examination in Phase II/III trials. Therefore, a clinical Phase II/III study (NCT04830371) was conducted to evaluate its efficacy in healthy Filipino participants aged 6 months to 45 years through administration of the test vaccine (Arm A, B, and C) or comparator vaccine Typbar-TCV® (Arm D). Sera samples were collected pre-vaccination (Visit 1) and post-vaccination (Visit 4, Day 28) to assess the immunogenicity of EuTCV and Typbar-TCV®. During the study, participants were regularly monitored through scheduled visits to the clinic to report any adverse events associated with the vaccine. For vaccine safety, the proportion of solicited and unsolicited Treatment-Emergent Adverse Events was all comparable between EuTCV and Typbar-TCV® groups. A single dose of EuTCV produced seroconversion in 99.4% of treated participants, with seroconversion rates non-inferior to that of Typbar-TCV®. Batch-to-batch consistency was concluded based on the 90% Confidence Interval of the geometric mean ratio (EuTCV Arm A, B, and C) at Week 4, lying within the equivalence margin of 0.5 to 2.0 for all batches. Results from this Phase II/III clinical trial of EuTCV in healthy volunteers show comparable safety and considerable immunogenicity, compared to Typbar-TCV®, meeting the objectives of this pivotal study. ClinicalTrials.gov registration number: NCT04830371.

Chung Hun Wha Dam Tang attenuates atherosclerosis in apolipoprotein E-deficient mice via the NF-κB pathway.

Chung Hun Wha Dam Tang (CHWDT), a traditional Korean herbal formula, has been used for hundreds of years for alleviating dizziness, phlegm, and inflammation. The inhibitory effects of CHWDT on obesity have been reported. However, the effects of CHWDT in atherosclerosis have not yet been explored. Therefore, the aim of the study was to investigate whether CHWDT could confer protection from oxidative stress and inflammation in a high fat diet (HFD)-induced atherosclerosis model. Atherosclerosis was induced by feeding ApoeE-/- mice with HFD for 6 weeks. To examine the in vivo effects of CHWDT on HFD-induced atherosclerosis, mice on HFD for 6 weeks were orally administrated with CHWDT (400 or 800 mg/kg) every other day for an additional 6 weeks and histological features of aorta were determined by Sudan IV and H&E staining. The mRNA levels of TNF-α, SOD1, SOD2, iNOS or eNOS were determined with RT-PCR analysis or western blot analysis for protein levels. ROS generation was measured by CM-2DCFDA or MitoSox staining using FACS analysis or confocal microscopy. CHWDT decreased the mRNA levels of TNF-α and increased the mRNA levels of SOD1, SOD2 and catalase in both aorta and liver tissues of atherosclerotic mice. CHWDT attenuated TNF-α and iNOS expression in RAW 264.7 cells, U937 cells and HUVECs, and restored eNOS expression in HUVECs. CHWDT decreased H2O2-induced cellular ROS generation in RAW 264.7 cells and U937 cells, and also decreased H2O2-induced mitochondrial ROS generation in RAW 264.7 cells. Furthermore, SOD1, SOD2 and catalase mRNA levels were increased by pre-treatment with CHWDT in H2O2 and LPS-stimulated RAW 264.7 cells, as well as in LPS-treated U937 and HUVECs. CHWDT not only decreased LPS-induced NF-κB p65 phosphorylation but also inhibited the translocation of p65 from the cytosol to the nucleus in RAW 264.7 macrophages. These results suggest that CHWDT exerts inhibitory effects on atherosclerosis-induced oxidative stress and inflammation via the NF-κB pathway.