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

Autor: Ataullakhanov Ravshan I, Olga A. Smirnova, Natalia Petrakova, Maria G. Isaguliants, Alla A. Kushch, O. V. Masalova, Alexander V. Ivanov, E. I. Lesnova, Vadim V. Grabovetsky, Tatiana Mikhailovna Melnikova, A.V. Pichugin, Alexei D. Zaberezhny
Rok vydání: 2010
Předmět:
Zdroj: Vaccine. 28:1987-1996
ISSN: 0264-410X
DOI: 10.1016/j.vaccine.2009.10.097
Popis: 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.
Databáze: OpenAIRE