Dual-Antigen COVID-19 Vaccine Subcutaneous Prime Delivery With Oral Boosts Protects NHP Against SARS-CoV-2 Challenge.

We have developed a dual-antigen COVID-19 vaccine incorporating genes for a modified SARS-CoV-2 spike protein (S-Fusion) and the viral nucleocapsid (N) protein with an Enhanced T-cell Stimulation Domain (N-ETSD) to increase the potential for MHC class II responses. The vaccine antigens are delivered by a human adenovirus serotype 5 platform, hAd5 [E1-, E2b-, E3-], previously demonstrated to be effective in the presence of Ad immunity. Vaccination of rhesus macaques with the hAd5 S-Fusion + N-ETSD vaccine by subcutaneous prime injection followed by two oral boosts elicited neutralizing anti-S IgG and T helper cell 1-biased T-cell responses to both S and N that protected the upper and lower respiratory tracts from high titer (1 x 106 TCID50) SARS-CoV-2 challenge. Notably, viral replication was inhibited within 24 hours of challenge in both lung and nasal passages, becoming undetectable within 7 days post-challenge.

C/EBPdelta is a downstream mediator of IL-6 induced growth inhibition of prostate cancer cells.

BACKGROUND: Although a number of reports have investigated the effects of IL-6 family cytokines on prostate cell growth, there is limited information available identifying IL-6 inducible downstream effector genes and their function in growth control. Previous studies have demonstrated that IL-6 treatment results in the activation of signal transducer and activator of transcription3 (STAT3) in prostate cancer cells. The goal of this study was to investigate the influence of IL-6 treatment and activation of the Jak/STAT signal transduction pathway on C/EBPdelta gene expression and growth inhibition of human prostate cancer cells. METHODS: Expression of C/EBPdelta and STAT3 activation were assayed using Northern and Western blotting techniques. Proliferation was assessed by [(3)H] thymidine incorporation, flow cytometry, and colony formation analyses. The analysis of the transcriptional regulation of C/EBPdelta was performed using luciferase-reporter constructs. RESULTS: In this report, we demonstrate that IL-6 treatment induces STAT3 activation (pSTAT3), pSTAT3 binds to the human C/EBPdelta gene promoter and induces its expression. We also demonstrate that C/EBPdelta over-expression is capable of suppressing prostate cancer cell growth. CONCLUSIONS: These results demonstrate that C/EBPdelta gene expression is increased in IL-6 treated LNCaP cells. Increased C/EBPdelta gene expression plays an important role in IL-6/STAT3 mediated growth arrest of LNCaP prostate cancer cells. Ongoing studies are investigating the mechanism by which C/EBPdelta controls prostate cancer cell growth and the potential role of C/EBPdelta in the survival and chemo resistance of prostate cancer metastasis. (c) 2004 Wiley-Liss, Inc.