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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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 Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
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(xsd:dateTime)
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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