The successful immune response against hepatitis C nonstructural protein 5A (NS5A) requires heterologous DNA/protein immunization.
The aim of this study was to evaluate the immunogenicity of NS5A protein of human hepatitis C virus (HCV) when delivered as naked DNA (NS5A DNA), or recombinant protein (rNS5A). DBA/2J mice received NS5A DNA, rNS5A, or NS5A DNA/rNS5A in different prime-boost combinations with a peptidoglycan Immunomax((R)). The weakest response was induced after rNS5A prime and NS5A DNA boost; rNS5A alone induced an immune response with a strong Th2-component; and NS5A DNA alone, a relatively weak secretion of IL-2 and IFN-gamma. The most efficient was co-injection of NS5A DNA and rNS5A, which induced a significant increase in CD4(+) and CD8(+) T-cell counts, anti-NS5A antibodies, specific T-cell proliferation, and proinflammatory cytokine production in vitro against a broad spectrum of NS5A epitopes. Administration of the mixture of adjuvanted DNA and protein immunogens can be selected as the best regimen for further preclinical HCV-vaccine trials.
Masalova
Olga V
OV
D.I. Ivanovsky Institute of Virology, Russian Academy of Medical Sciences, Gamaleya str. 16, 123098 Moscow, Russian Federation. ol.mas@mail.ru
Lesnova
Ekaterina I
EI
Pichugin
Alexei V
AV
Melnikova
Tatiana M
TM
Grabovetsky
Vadim V
VV
Petrakova
Natalia V
NV
Smirnova
Olga A
OA
Ivanov
Alexander V
AV
Zaberezhny
Alexei D
AD
Ataullakhanov
Ravshan I
RI
Isaguliants
Maria G
MG
Kushch
Alla A
AA
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation; D000939:Epitopes / Q000276:immunology; D005260:Female; D006526:Hepatitis C / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D010457:Peptidoglycan / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000276:immunology*; D012324:RNA-Dependent RNA Polymerase
D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D000939:Epitopes; D007371:Interferon-gamma; D007376:Interleukin-2; D010457:Peptidoglycan; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase