Cucumber mosaic virus as a presentation system for a double hepatitis C virus-derived epitope.
Chimeric plant viruses are emerging as promising vectors for use in innovative vaccination strategies. In this context, cucumber mosaic virus (CMV) has proven to be a suitable carrier of the hepatitis C virus (HCV)-derived R9 mimotope. In the present work, a new chimeric CMV, expressing on its surface the HCV-derived R10 mimotope, was produced but lost the insert after the first passage on tobacco. A comparative analysis between R10- and R9-CMV properties indicated that R9-CMV stability was related to structural features typical of the foreign insert. Thus, in order to combine high virus viability with strong immuno-stimulating activity, we doubled R9 copies on each of the 180 coat protein (CP) subunits of CMV. One of the chimeras produced by this approach (2R9-CMV) was shown to systemically infect the host, stably maintaining both inserts. Notably, it was strongly recognized by sera of HCV-infected patients and, as compared with R9-CMV, displayed an enhanced ability to stimulate lymphocyte IFN-gamma production. The high immunogen levels achievable in plants or fruits infected with 2R9-CMV suggest that this chimeric form of CMV may be useful in the development of oral vaccines against HCV.
Nuzzaci
M
M
Department of Biology, Plant Protection and Agrobiotechnology, University of Basilicata, Potenza, Italy.
Piazzolla
G
G
Vitti
A
A
Lapelosa
M
M
Tortorella
C
C
Stella
I
I
Natilla
A
A
Antonaci
S
S
Piazzolla
P
P
D000595:Amino Acid Sequence; D000918:Antibody Specificity; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D017799:Cucumovirus / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005822:Genetic Vectors / Q000378:metabolism*; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D030821:Plants, Genetically Modified / Q000378:metabolism*; D016865:Reassortant Viruses / Q000378:metabolism*; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D016415:Sequence Alignment; D014761:Viral Hepatitis Vaccines / Q000235:genetics* / Q000276:immunology
D036022:Capsid Proteins; D000939:Epitopes; D007106:Immune Sera; D010455:Peptides; D011994:Recombinant Proteins; D014761:Viral Hepatitis Vaccines; D007371:Interferon-gamma