Individual expression and processing of hepatitis C virus E1/ E2 epitopes-based DNA vaccine candidate in healthy humans' peripheral blood mononuclear cells

被引:1
作者
Nadeem, Rola [1 ,2 ]
Maghraby, Amany Sayed [1 ,2 ]
Abd-Elshafy, Dina Nadeem [2 ,3 ]
Barakat, Ahmed Barakat [4 ]
Bahgat, Mahmoud Mohamed [1 ,2 ,5 ]
机构
[1] Natl Res Ctr, Pharmaceut & Drug Ind Res Inst, Dept Therapeut Chem, Cairo, Egypt
[2] Natl Res Ctr, Ctr Excellence Adv Sci, Immune & Biomarkers Infect Res Grp, Cairo, Egypt
[3] Natl Res Ctr, Environm Res Inst, Dept Water Pollut Res, Cairo, Egypt
[4] Ain Shams Univ, Fac Sci, Microbiol Dept, Cairo, Egypt
[5] Natl Res Ctr, Ctr Excellence Adv Sci, Immune & Bio Markers Infect Res Grp, El Buhooth St Formerly El Tahrir, Cairo 12622, Egypt
关键词
Hepatitis C virus; DNA vaccines; Human peripheral blood mononuclear cells; Individuality; Envelope protein; HUMAN MONOCLONAL-ANTIBODIES; NEUTRALIZING ANTIBODIES; ENVELOPE GLYCOPROTEIN; INFECTION; HCV; IMMUNOGENICITY; CARCINOMA; RESPONSES; RECEPTOR;
D O I
10.7774/cevr.2023.12.1.47
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Purpose: The development and study of hepatitis C virus (HCV) vaccine candidates' individu-alized 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 pro-cessing 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 expres-sion 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 as-say. Two groups, five Swiss albino mice each, were immunized with the EC or a control con-struct. 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.
引用
收藏
页码:47 / 59
页数:13
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