[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 response against hepatitis C virus].
Hepatitis C is related to the most important socially significant human infectious diseases; however, vaccine against this virus up to now has notbeen created. One of the possible components of vaccine is the nonstructural protein NS3 of hepatitis C virus (HCV), which is synthesized in the infected cells and displays protease, NTPase, and helicase enzymatic activities. The connection between the effectiveness ofT cellular response to NS3 epitopes and the spontaneous resolution of acute hepatitis C was shown. The purpose of this work was to compare the immune response of mice to the inoculation of nucleotide and amino acid sequences of HCV NS3 and their combination, to evaluate the adjuvant activity of the DNA encoding granulocyte macrophage colony-stimulating factor (GM-CSF) and the influence of regulatory T cells on the effectiveness of immune response. The maximum anti-HCV NS3 antibody level in the serum (to 1:640000) induced the recombinant protein rNS3 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-gamma-secreting cells and IFN-gamma, and IL-2 release in response to the stimulators--NS3 antigens of different composition were observed in this group of mice. It has been established that the suppression of regulatory T cells in vitro leads to the statistically significant increase in the secretion of IFN-gamma. Thus, simultaneous application of rNS3 along with the DNAs encoding full-size NS3 and GM-CSF is promising approach for development of hepatitis C vaccine. The expediency of inclusion in the vaccine composition of regulatory T cell inhibitors will be clear after special studies.
O V
OV
Masalova
E I
EI
Lesnova
L N
LN
Shingarova
V L
VL
Tunitskaia
T I
TI
Ulanova
A N
AN
Burkov
A A
AA
Kushch
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D000917:Antibody Formation; D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D014709:Vero Cells; D014761:Viral Hepatitis Vaccines / Q000235:genetics / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000276:Adjuvants, Immunologic; D000536:Aluminum Hydroxide; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D018076:DNA, Complementary; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D007376:Interleukin-2; D011994:Recombinant Proteins; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases