The successful immune response against hepatitis C nonstructural protein 5A (NS5A) requires heterologous DNA/protein immunization |
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Authors: | Olga V Masalova Ekaterina I Lesnova Alexei V Pichugin Tatiana M Melnikova Vadim V Grabovetsky Natalia V Petrakova Olga A Smirnova Alexander V Ivanov Alexei D Zaberezhny Ravshan I Ataullakhanov Maria G Isaguliants Alla A Kushch |
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Institution: | 1. D.I. Ivanovsky Institute of Virology, Russian Academy of Medical Sciences, Gamaleya str. 16, 123098 Moscow, Russian Federation;2. Institute of Immunology, Russian Ministry of Health, Kashirskoe shosse 24, 115478 Moscow, Russian Federation;3. Immapharma Ltd., Gamaleya str. 18, 123098 Moscow, Russian Federation;4. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str. 32, 119991 Moscow, Russian Federation;5. Department of Virology, Swedish Institute for Infectious Disease Control, 17182 Stockholm, Sweden |
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Abstract: | 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®. 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-γ. 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. |
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Keywords: | Hepatitis C virus HCV vaccine Nonstructural protein 5A (NS5A) DNA immunization Heterologous prime-boost Promiscuous T-cell epitopes Adjuvant Immunomax |
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