Individual expression and processing of hepatitis C virus E1/E2 epitopes-based DNA vaccine candidate in healthy humans’ peripheral blood mononuclear cells
10.7774/cevr.2023.12.1.47
- Author:
Rola NADEEM
1
;
Amany Sayed MAGHRABY
;
Dina Nadeem ABD-ELSHAFY
;
Ahmed Barakat BARAKAT
;
Mahmoud Mohamed BAHGAT
Author Information
1. Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute, National Research Center, Cairo, Egypt
- Publication Type:Original Article
- From:Clinical and Experimental Vaccine Research
2023;12(1):47-59
- CountryRepublic of Korea
- Language:English
-
Abstract:
Purpose:The development and study of hepatitis C virus (HCV) vaccine candidates’ individualized responses are of great importance. Here we report on an HCV DNA vaccine candidate based on selected envelope (E1/E2) epitopes. Besides, we assessed its expression and processing in human peripheral blood mononuclear cells (PBMCs) and in vivo cellular response in mice.
Materials and Methods:HCV E1/E2 DNA construct (EC) was designed. The antigen expression of EC was assayed in PBMCs of five HCV-uninfected donors via a real-time quantitative polymerase chain reaction. Serum samples from 20 HCV antibody-positive patients were used to detect each individual PBMCs expressed antigens via enzyme-linked immunosorbent assay. Two groups, five Swiss albino mice each, were immunized with the EC or a control construct. The absolute count of lymph nodes’ CD4+ and CD8+ T-lymphocytes was assessed.
Results:Donors’ PBMCs showed different levels of EC expression, ranging between 0.83–2.61-fold in four donors, while donor-3 showed 34.53-fold expression. The antigens expressed in PBMCs were significantly reactive to the 20 HCV antibody repertoire (all p=0.0001). All showed comparable reactivity except for donor-3 showing the lowest reactivity level. The absolute count % of the CD4+ T-cell significantly increased in four of the five EC-immunized mice compared to the control group (p=0.03). No significant difference in CD8+ T-cells % was observed (p=0.89).
Conclusion:The inter-individual variation in antigen expression and processing dominance was evident, showing independence in individuals’ antigen expression and reactivity levels to antibodies. The described vaccine candidate might result in a promising natural immune response with a possibility of CD4+ T-cell early priming.
