The successful immune response against hepatitis C nonstructural protein 5A (NS5A) requires heterologous DNA/protein immunization

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• 作者：Olga V. Masalova ; Ekaterina I. Lesnova ; Alexei V. Pichugin ; Tatiana M. Melnikova ; Vadim V. Grabovetsky ; Natalia V. Petrakova ; Olga A. Smirnova ; Alex ; er V. Ivanov ; Alexei D. Zaberezhny ; Ravshan I. Atau
• 关键词：Hepatitis C virus ; HCV vaccine ; Nonstructural protein 5A (NS5A) ; DNA immunization ; Heterologous prime-boost ; Promiscuous T-cell epitopes ; Adjuvant ; Immunomax
• 刊名：Vaccine
• 出版年：2010
• 出版时间：23 February 2010
• 年：2010
• 卷：28
• 期：8
• 页码：1987-1996
• 全文大小：900 K

文摘

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.