Abstract
BackgroundVaccination against HCV is an effective measure in reduction of virus-related public health burden and mortality. However, no prophylactic vaccine is available as of yet. DNA-based immunization is a promising modality to generate cellular and humoral immune responses. The objective of this study is to provide a systematic review of HCV DNA vaccines and investigate and discuss the strategies employed to optimize their efficacies.MethodsMEDLINE (PubMed), Web of Science, Scopus, ScienceDirect, and databases in persian language including the Regional Information Centre for Science & Technology (RICeST), the Scientific Information Database and the Iranian Research Institute for Information Science and Technology (IranDoc) were examined to identify studies pertaining to HCV nucleic acid vaccine development from 2000 to 2020.ResultsTwenty-seven articles were included. Studies related to HCV RNA vaccines were yet to be published. A variety of strategies were identified with the potential to optimize HCV DNA vaccines such as incorporating multiple viral proteins and molecular tags such as HBsAg and Immunoglobulin Fc, multi-epitope expression, co-expression plasmid utilization, recombinant subunit immunogens, heterologous prime-boosting, incorporating NS3 mutants in DNA vaccines, utilization of adjuvants, employment of less explored methods such as Gene Electro Transfer, construction of multi- CTL epitopes, utilizing co/post translational modifications and polycistronic genes, among others. The effectiveness of the aforementioned strategies in boosting immune response and improving vaccine potency was assessed.ConclusionsThe recent progress on HCV vaccine development was examined in this systematic review to identify candidates with most promising prophylactic and therapeutic potential.
Highlights
Vaccination against Hepatitis C virus (HCV) is an effective measure in reduction of virus-related public health burden and mortality
Among the established vaccine types, a number of experimental nucleic acid-based vaccines are being developed which are mostly directed at inducing antibodies and cytotoxic T lymphocyte (CTL) responses against the non-struc‐ tural proteins and envelope proteins of the virus
The keywords and terms used to find articles rel‐ evant to DNA immunization included ‘Hepatitis C Virus and DNA vaccine’, ‘HCV DNA vaccine and development’, ‘HCV DNA vaccine and Adjuvant’, ‘HCV DNA vaccine and Antigenic target’, ‘HCV DNA vaccine and Immuno‐ genicity’, ‘HCV DNA vaccine and efficiency’
Summary
Vaccination against HCV is an effective measure in reduction of virus-related public health burden and mortality. To improve the effectiveness of the vac‐ cines, several studies have been carried out to assess the efficacy of a variety of modifications in improving vaccine potency In this regard, the use of truncated form of the highly immunogenic NS3 protein [12], taking advantage of vector-based and plasmids vaccines [13, 14], exploring prime-boost regimens with DNA and recombinant virus vaccines [15], utilizing multi-epitope DNA and peptide vaccines and novel techniques such as Gene Electrotrans‐ fer [16, 17], development of multigenotype vaccines [18], and inclusion of genetic adjuvants such as Human and avian hepatitis B virus (HBV) core antigen (HBcAg) [19], perforin (PRF) [20], heat shock protein gp96 [21], CCchemokine ligand 20 (CCL20) gene [22], Interleukin-12 (IL-12) [23], IL-23, granulocyte-monocyte colony stimu‐ lating factor (GM-CSF) [24], etc. The use of truncated form of the highly immunogenic NS3 protein [12], taking advantage of vector-based and plasmids vaccines [13, 14], exploring prime-boost regimens with DNA and recombinant virus vaccines [15], utilizing multi-epitope DNA and peptide vaccines and novel techniques such as Gene Electrotrans‐ fer [16, 17], development of multigenotype vaccines [18], and inclusion of genetic adjuvants such as Human and avian hepatitis B virus (HBV) core antigen (HBcAg) [19], perforin (PRF) [20], heat shock protein gp96 [21], CCchemokine ligand 20 (CCL20) gene [22], Interleukin-12 (IL-12) [23], IL-23, granulocyte-monocyte colony stimu‐ lating factor (GM-CSF) [24], etc. have been explored in previous studies
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