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Utilizing the Antigen Capsid-Incorporation Strategy for the Development of Adenovirus Serotype 5-Vectored Vaccine Approaches
Published on: May 6, 2015
The successful immune response against hepatitis C nonstructural protein 5A (NS5A) requires heterologous DNA/protein
Olga V Masalova1, Ekaterina I Lesnova, Alexei V Pichugin
1D.I. Ivanovsky Institute of Virology, Russian Academy of Medical Sciences, Gamaleya str. 16, 123098 Moscow, Russian Federation. ol.mas@mail.ru
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((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.
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