Comparison of the inhibitory and stimulatory effects of Core and NS3 candidate HCV vaccines on the cellular immune response.

Abstract

Currently, hepatitis C virus (HCV) infects nearly 3% of the global population, the majority of whom are chronically infected; however, hepatitis C vaccines are still in the developmental stage. Numerous studies suggest that the spontaneous resolution of HCV infection and the design of its vaccine are reliant on vital contributions from CTL cell responses and T regulatory cells. Multiple researchers have identified both Core and nonstructural protein 3 (NS3) proteins as crucial immune genes and potential candidates for HCV DNA vaccine design. In this study, Core and NS3 were subcloned and inserted into pcDNA3.1 to construct HCV DNA vaccines administered in mouse models. Furthermore, the effects of Core and NS3 on the induction of CTL and NK were compared in spleen mouse models using the LDH method. Additionally, flow cytometry was employed to investigate the percentage of T regulatory cells (Treg cells) and cells expressing PD-1 in the spleens of the mouse models. Our data indicated that pcDNA3.1+NS3 and pcDNA3.1+Core could enhance CTL and NK activity in mouse models. Importantly, the Treg and PD-1 analysis in mouse models revealed a substantial reduction in the proportions of CD4+/CD25+/Foxp3+ T cells and PD-1+ cells in experimental subjects treated with HCV NS3 along with 5 mg/kg of lenalidomide, utilized as a novel adjuvant, compared to those administered an equivalent dosage of lenalidomide in conjunction with HCV Core. In conclusion, our observations indicated that the NS3-HCV gene had a limited impact on the activation of inhibitory factors. Therefore, NS3 is considered a more suitable candidate for DNA vaccine design compared to Core HCV.