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About:
Enhancement of the expression of HCV core gene does not enhance core-specific immune response in DNA immunization: advantages of the heterologous DNA prime, protein boost immunization regimen
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wasabi.inria.fr
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research paper
schema:ScholarlyArticle
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type
Academic Article
research paper
schema:ScholarlyArticle
isDefinedBy
Covid-on-the-Web dataset
has title
Enhancement of the expression of HCV core gene does not enhance core-specific immune response in DNA immunization: advantages of the heterologous DNA prime, protein boost immunization regimen
Creator
Alekseeva, Ekaterina
Bruvere, Ruta
Egorova, Irina
Isaguliants, Maria
Kozlovskaya, Tatyana
Kushners, Eriks
Mihailova, Marija
Petrakova, Natalia
Pumpens, Paul
Skrastina, Dace
Sominskaya, Irina
Starodubova, Elizaveta
Source
Medline; PMC
abstract
BACKGROUND: Hepatitis C core protein is an attractive target for HCV vaccine aimed to exterminate HCV infected cells. However, although highly immunogenic in natural infection, core appears to have low immunogenicity in experimental settings. We aimed to design an HCV vaccine prototype based on core, and devise immunization regimens that would lead to potent anti-core immune responses which circumvent the immunogenicity limitations earlier observed. METHODS: Plasmids encoding core with no translation initiation signal (pCMVcore); with Kozak sequence (pCMVcoreKozak); and with HCV IRES (pCMVcoreIRES) were designed and expressed in a variety of eukaryotic cells. Polyproteins corresponding to HCV 1b amino acids (aa) 1–98 and 1–173 were expressed in E. coli. C57BL/6 mice were immunized with four 25-μg doses of pCMVcoreKozak, or pCMV (I). BALB/c mice were immunized with 100 μg of either pCMVcore, or pCMVcoreKozak, or pCMVcoreIRES, or empty pCMV (II). Lastly, BALB/c mice were immunized with 20 μg of core aa 1–98 in prime and boost, or with 100 μg of pCMVcoreKozak in prime and 20 μg of core aa 1–98 in boost (III). Antibody response, [(3)H]-T-incorporation, and cytokine secretion by core/core peptide-stimulated splenocytes were assessed after each immunization. RESULTS: Plasmids differed in core-expression capacity: mouse fibroblasts transfected with pCMVcore, pCMVcoreIRES and pCMVcoreKozak expressed 0.22 ± 0.18, 0.83 ± 0.5, and 13 ± 5 ng core per cell, respectively. Single immunization with highly expressing pCMVcoreKozak induced specific IFN-γ and IL-2, and weak antibody response. Single immunization with plasmids directing low levels of core expression induced similar levels of cytokines, strong T-cell proliferation (pCMVcoreIRES), and antibodies in titer 10(3)(pCMVcore). Boosting with pCMVcoreKozak induced low antibody response, core-specific T-cell proliferation and IFN-γ secretion that subsided after the 3rd plasmid injection. The latter also led to a decrease in specific IL-2 secretion. The best was the heterologous pCMVcoreKozak prime/protein boost regimen that generated mixed Th1/Th2-cellular response with core-specific antibodies in titer ≥ 3 × 10(3). CONCLUSION: Thus, administration of highly expressed HCV core gene, as one large dose or repeated injections of smaller doses, may suppress core-specific immune response. Instead, the latter is induced by a heterologous DNA prime/protein boost regimen that circumvents the negative effects of intracellular core expression.
has issue date
2009-06-08
(
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)
bibo:doi
10.1186/1479-0556-7-7
bibo:pmid
19505299
has license
cc-by
sha1sum (hex)
9ad61dcfb0a71ebe88c497995cf569eba5e73f8c
schema:url
https://doi.org/10.1186/1479-0556-7-7
resource representing a document's title
Enhancement of the expression of HCV core gene does not enhance core-specific immune response in DNA immunization: advantages of the heterologous DNA prime, protein boost immunization regimen
has PubMed Central identifier
PMC2702340
has PubMed identifier
19505299
schema:publication
Genet Vaccines Ther
resource representing a document's body
covid:9ad61dcfb0a71ebe88c497995cf569eba5e73f8c#body_text
is
schema:about
of
named entity 'immunization'
named entity 'HCV'
named entity 'REGIMEN'
named entity 'HETEROLOGOUS'
named entity 'THERAPY'
named entity 'CELLS'
named entity 'DEVISE'
named entity 'SETTINGS'
named entity 'HEPATITIS C'
named entity 'CORE PROTEIN'
named entity 'HCV'
named entity 'IMMUNOGENIC'
named entity 'OBSERVED'
named entity 'BASED'
named entity 'ATTRACTIVE'
named entity 'BACKGROUND'
named entity 'LEAD'
named entity 'EARLIER'
named entity 'PROTEIN '
named entity 'HIGHLY'
named entity 'HAVE'
named entity 'IMMUNOGENICITY'
named entity 'VACCINE'
named entity 'IMMUNE RESPONSES'
named entity 'DNA'
named entity 'EXPRESSION'
named entity 'VACCINES'
named entity 'ENHANCEMENT'
named entity 'ENHANCE'
named entity 'TARGET'
named entity 'IMMUNIZATION'
named entity 'INFECTED'
named entity 'DNA IMMUNIZATION'
named entity 'CORE'
named entity 'DOES NOT'
named entity 'SPECIFIC IMMUNE RESPONSE'
named entity 'PROTEIN '
named entity 'GENE'
named entity 'IMMUNIZATION'
named entity 'GENETIC'
named entity 'LIMITATIONS'
named entity 'DESIGN'
named entity 'NATURAL INFECTION'
named entity 'LOW'
named entity 'PROTOTYPE'
named entity 'CORE'
named entity 'BOOST'
named entity 'HCV'
named entity 'PRIME'
named entity 'REGIMENS'
named entity 'EXPERIMENTAL'
covid:arg/9ad61dcfb0a71ebe88c497995cf569eba5e73f8c
named entity 'cells'
named entity 'Background'
named entity 'However'
named entity 'advantages'
named entity 'immune responses'
named entity 'vaccine'
named entity 'immunogenic'
named entity 'vaccine'
named entity 'experimental settings'
named entity 'immunization'
named entity 'HCV'
named entity 'attractive'
named entity 'Microbiology'
named entity 'IgG2'
named entity 'HCV'
named entity 'peptide'
named entity 'HCV'
named entity 'T-cell stimulation'
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