The combined application of nucleotide and amino acid sequences of NS3 hepatitis C virus protein, DNA encoding granulocyte macrophage colony-stimulating factor, and inhibitor of regulatory T cells induces effective immune responce against Hepatitis C virus

• Published in: Molecular biology (New York) Vol. 46; no. 3; pp. 473 - 480
• Main Authors: Masalova, O. V., Lesnova, E. I., Shingarova, L. N., Tunitskaya, V. L., Ulanova, T. I., Burkov, A. N., Kushch, A. A.
• Format: Journal Article
• Language: English
• Published: Dordrecht SP MAIK Nauka/Interperiodica 01-05-2012; Springer Nature B.V
• Subjects: Adjuvants; Aluminum hydroxide; Amino acids; Antibodies; Biochemistry; Biomedical and Life Sciences; Cell proliferation; Deoxyribonucleic acid; DNA; DNA helicase; Enzymatic activity; Epitopes; gamma -Interferon; Granulocyte-macrophage colony-stimulating factor; Hepatitis; Hepatitis C; Hepatitis C virus; Human Genetics; Immunology; Immunoregulation; Infectious diseases; Inoculation; Interleukin 2; Life Sciences; Lymphocytes T; Molecular Biomedicine Special Issue; Nonstructural proteins; Nucleotide sequence; Proteinase; Proteins; Statistical analysis; T cell receptors; Vaccines; regulatory T cells; granulocyte macrophage colony-stimulating factor; DNA immunization; nonstructural protein NS3; immune response; recombinant protein; transfection; hepatitis C virus
• ISSN: 0026-8933; 1608-3245
• DOI: 10.1134/S0026893312030077

Hepatitis C is related to the most important socially significant human infectious diseases. However, there is no vaccine for the hepatitis C virus. The nonstructural protein NS3 of the hepatitis C virus (HCV), which is synthesyzed in the infected cells and it displays protease, NTPase, and helicase enzymatic activities, is one of the possible components of the vaccine. The connection between the effectiveness of the T-cell response to NS3 epitopes and the spontaneous resolution of acute hepatitis C has been shown. The purpose of this work was to compare the immune response of mice to the inoculation of the nucleotide and amino acid sequences of HCV NS3 and their combination, as well as to evaluate the adjuvant activity of the DNA encoding of granulocyte macrophage colony-stimulating factor (GM-CSF) and the influence of regulatory T cells on the effectiveness of the immune response. The maximum anti-HCV NS3 antibody level in the serum (up to 1: 640000) induced the recombinant rNS3 protein introduced with aluminum hydroxide. The most intensive cellular immune response was observed after the simultaneous administration of rNS3 and DNAs encoding full-size NS3 and GM-CSF. A high level of lymphocyte proliferation, accumulation of IFN-γ-secreting cells, and IFN-γ/IL-2 release in response to the stimulators (NS3 antigens of different compositions) were observed in this group of mice. It has been established that the in vitro suppression of regulatory T cells leads to a statistically significant increase in the secretion of IFN-γ. Thus, the simultaneous application of rNS3, along with the DNAs encoding full-size NS3 and GM-CSF, is a promising approach to the development of hepatitis C vaccine. The expediency of adding regulatory T-cell inhibitors in the vaccine composition will be clear after special studies.