Hepatitis C virus DNA vaccines: a systematic review

Abstract

Background Vaccination 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. Methods MEDLINE (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. Results Twenty-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. Conclusions The recent progress on HCV vaccine development was examined in this systematic review to identify candidates with most promising prophylactic and therapeutic potential.

Future Prospects, Approaches, and the Government’s Role in the Development of a Hepatitis C Virus Vaccine

“…The triple doses of peptide vaccine induced a higher level of IFN-γ/IL-4 ratio as compared to other tested combinations [47]. Another study has indicated that the vaccination of BALB/c mice with a dose of 800 ng to 16 µg of multiple antigenic peptides made by combining conserved epitopes of HCV E1, E2, NS4B, NS5A, and NS5B has produced elevated immunogenic responses and caused an induction of IFN-γ-producing CD4+/CD8+ T-lymphocytes in the immunized mice [15,48].…”

“…The continuous advancement of global research has provided significant and valuable insights into the structural and non-structural proteins of HCV to identify the main targets and epitopes for effective HCV vaccine design and development. While the Core, E1, and E2 proteins have been predominantly utilized as vaccine targets compared to the nonstructural proteins, ongoing efforts aim to explore the full potential of these proteins in HCV vaccine design [12][13][14][15][16][17][18][19][20][21][22][23][24][25]. The ORF encodes a single polyprotein of approximately 3030 amino acids, which is processed co-and post-translationally by various cellular and viral proteases into three structural proteins (Core, E1, and E2) at the N-terminus and seven non-structural proteins (P7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B) at the C-terminus.…”

“…The E2 protein has emerged as a prominent target for the development of HCV-specific neutralizing antibodies (nAbs) compared with other proteins, [13,15,22]. The full-length structure of the E2 ectodomain was successfully resolved by several research groups, providing significant structural insights for the development of the HCV vaccine.…”

Development of therapeutic vaccines for the treatment of diseases

“…Plasmid DNA encoding antigenic HCV protein(s) or epitope(s) can induce both humoral and cellular immune responses in vivo [ 132 ]. DNA vaccines include the nucleotides encoding structural proteins or nonstructural proteins, such as NS3, NS4, NS5, core, and the envelope proteins E1/E2 [ 133 ]. CIGB-230, containing a mixture of core/E1/E2-expressing plasmids, was the first therapeutic DNA vaccine for HCV evaluated in clinical trials [ 134 , 135 ].…”

A close view of the Hepatitis C virus vaccines with further perspective

“…Hepatitis C virus (HCV) is a serious international health threat that persistently infects around 170 million individuals worldwide (∼2% of the world's population). It is estimated that there are three to four million people are infected with HCV annually; the majority of HCV-infected cases remain undetected as chronic HCV carriers because HCV infection barely presented with clinical manifestation earlier than the onset of advanced liver disease stage [ 1 ]. Chronic infection with HCV is associated with end-stage liver disease e.g.…”