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

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...

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Autores principales: Nadeem, Rola, Maghraby, Amany Sayed, Abd-Elshafy, Dina Nadeem, Barakat, Ahmed Barakat, Bahgat, Mahmoud Mohamed
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Vaccine Society 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9950224/
https://www.ncbi.nlm.nih.gov/pubmed/36844691
http://dx.doi.org/10.7774/cevr.2023.12.1.47
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author Nadeem, Rola
Maghraby, Amany Sayed
Abd-Elshafy, Dina Nadeem
Barakat, Ahmed Barakat
Bahgat, Mahmoud Mohamed
author_facet Nadeem, Rola
Maghraby, Amany Sayed
Abd-Elshafy, Dina Nadeem
Barakat, Ahmed Barakat
Bahgat, Mahmoud Mohamed
author_sort Nadeem, Rola
collection PubMed
description 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.
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spelling pubmed-99502242023-02-25 Individual expression and processing of hepatitis C virus E1/E2 epitopes-based DNA vaccine candidate in healthy humans’ peripheral blood mononuclear cells Nadeem, Rola Maghraby, Amany Sayed Abd-Elshafy, Dina Nadeem Barakat, Ahmed Barakat Bahgat, Mahmoud Mohamed Clin Exp Vaccine Res Original Article 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. The Korean Vaccine Society 2023-01 2023-01-31 /pmc/articles/PMC9950224/ /pubmed/36844691 http://dx.doi.org/10.7774/cevr.2023.12.1.47 Text en © Korean Vaccine Society. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0 (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Nadeem, Rola
Maghraby, Amany Sayed
Abd-Elshafy, Dina Nadeem
Barakat, Ahmed Barakat
Bahgat, Mahmoud Mohamed
Individual expression and processing of hepatitis C virus E1/E2 epitopes-based DNA vaccine candidate in healthy humans’ peripheral blood mononuclear cells
title Individual expression and processing of hepatitis C virus E1/E2 epitopes-based DNA vaccine candidate in healthy humans’ peripheral blood mononuclear cells
title_full Individual expression and processing of hepatitis C virus E1/E2 epitopes-based DNA vaccine candidate in healthy humans’ peripheral blood mononuclear cells
title_fullStr Individual expression and processing of hepatitis C virus E1/E2 epitopes-based DNA vaccine candidate in healthy humans’ peripheral blood mononuclear cells
title_full_unstemmed Individual expression and processing of hepatitis C virus E1/E2 epitopes-based DNA vaccine candidate in healthy humans’ peripheral blood mononuclear cells
title_short Individual expression and processing of hepatitis C virus E1/E2 epitopes-based DNA vaccine candidate in healthy humans’ peripheral blood mononuclear cells
title_sort individual expression and processing of hepatitis c virus e1/e2 epitopes-based dna vaccine candidate in healthy humans’ peripheral blood mononuclear cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9950224/
https://www.ncbi.nlm.nih.gov/pubmed/36844691
http://dx.doi.org/10.7774/cevr.2023.12.1.47
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