Synthesis and Analysis of Properties of an Immunogenic Fragment from NS4A Polypeptide of Hepatitis C Virus

Abstract

Abstract— The work is aimed at the synthesis and analysis from NS4A of hepatitis C virus (HCV) antigen peptide fragment that contains a conserved B-cell and T-helper epitopes. The 24-mer peptide VIVGRIILSGRPAVIPDREVLYRK-NH2, which contains the main immunogenic site 24–46 of HCV NS4A antigen (corresponding to the 1681–1703 amino acid residues of the HCV polypeptide), subtype 1b, has been prepared via solid-phase synthesis according to the Fmoc-protocol. Particles with diameters of 73 ± 10 nm (30%) and 236 ± 5 nm (70%) have been detected in the water solution of the highly purified peptide (0.5 mg/mL) by dynamic light scattering. The polydispersity index of 0.377 ± 0.012 implies the existence of heterogeneity because of the aggregation of the peptide molecules. The ζ-potential of the peptide aggregates has been determined as 7.0 ± 0.5 mV by means of electrophoretic light scattering. These data confirm the possibility for the development of a nanoscale liposome form of the peptide preparation. Immunoreactivity of the synthesized highly purified peptide has been studied with the use of blood sera of patients with chronic hepatitis C. Antipeptide immunoglobulins G have been detected in 41.7% of serum samples. Thus, this peptide has been shown to reproduce at least one B-epitope, to which antibodies are raised during natural HCV infection. The synthesized 24-mer peptide is a promising candidate for further research and for use as a potential immunogen for the design of a nanoscale therapeutic immunogenic liposomal peptide composition with synthetic lipids as an adjuvant.

A Mixture of T-Cell Epitope Peptides Derived from Human Respiratory Syncytial Virus F Protein Conferred Protection in DR1-TCR Tg Mice

“…Peptide-based vaccines are synthesized in vitro by utilizing known immunogenic amino acid sequences, generally from B-cell or T-cell epitopes, and they have recently gained attention due to their ability to trigger both humoral and T-cell immune responses [ 23 , 24 , 25 ]. They have been used for the development of vaccines against various infectious diseases, including Malaria, influenza, HIV-1, SARS-CoV-2, and hepatitis C virus [ 23 , 26 , 27 , 28 ].…”

“…They have been used for the development of vaccines against various infectious diseases, including Malaria, influenza, HIV-1, SARS-CoV-2, and hepatitis C virus [ 23 , 26 , 27 , 28 ]. Vaccines based on T-cell epitope peptides focus T-cell responses on a specific set of critical epitopes, and the selection of minimal epitopes or short domains of the antigen of interest avoids the deleterious functions that are sometimes encountered when whole antigens are used [ 25 ]. The identification of immunogenic epitopes among the potential epitopes present in an antigenic protein is thus a critical step in attempts to optimize T-cell mediated immunity and is important for the development of efficient vaccines.…”

Binding of Natural Antibodies Generated after COVID-19 and Vaccination with Individual Peptides Corresponding to the SARS-CoV-2 S-Protein

“…Assessment of the immunodominance of individual epitopes in the plasma of recovered patients is of significant scientific interest compared to the immune response to natural infection and vaccination [19,20]. Such an evaluation would allow the selection of the most recognizable sequences for vaccine development.…”