- MeSH
- léková rezistence MeSH
- lidé MeSH
- malárie * epidemiologie prevence a kontrola MeSH
- Plasmodium patogenita MeSH
- příprava léků metody MeSH
- služby preventivní péče MeSH
- vakcína proti malárii farmakologie terapeutické užití MeSH
- vývoj vakcíny trendy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
In DNA vaccination, CD4(+) T-cell help can be enhanced by fusion of a gene encoding an immunization protein with a foreign gene or its part providing T(h) epitopes. To study the effect of helper epitope localization in a protein molecule, the influence of the vicinity of the helper epitope, and the impact of chimeric protein cellular localization, we fused the helper epitope p30 from tetanus toxin (TT, aa 947-967) with the N- or C-terminus of the mutated E7 oncoprotein (E7GGG) of human papillomavirus type 16, enlarged the p30 epitope with the flanking residues containing potential protease-sensitive sites and altered the cellular localization of the fusion constructs by signal sequences. The p30 epitope enhanced the E7-specific response, but only in constructs without added signal sequences. After localization of the fusion proteins into the endoplasmic reticulum and endo/lysosomal compartment, the TT-specific T(h)2 response was increased. The synthetic Pan DR epitope (PADRE) induced a stronger E7-specific response than the p30 epitope and its stimulatory effect was not limited to nuclear/cytoplasmic localization of the E7 antigen. These results suggest that in the optimization of immune responses by adding helper epitopes to DNA vaccines delivered by the gene gun, the cellular localization of the antigen needs to be taken into account.
- MeSH
- biolistika metody MeSH
- buňky NIH 3T3 MeSH
- cytokiny metabolismus MeSH
- DNA vakcíny aplikace a dávkování farmakologie MeSH
- endoplazmatické retikulum imunologie metabolismus MeSH
- HEK293 buňky MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- Papillomavirus E7 - proteiny genetika metabolismus farmakologie MeSH
- peptidové fragmenty genetika farmakologie MeSH
- plazmidy aplikace a dávkování MeSH
- rekombinantní fúzní proteiny metabolismus farmakologie MeSH
- tetanový toxin genetika farmakologie MeSH
- vakcína proti malárii farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The research in vaccine development is growing very intensively. More than 95 clinical trials of potential HIV vaccines have been performed in last 25 years. Currently, only two HIV vaccine candidates are in Phase III trials and one in Phase II trial. Tuberculosis is another problematic disease of the 21st century. Calmette-Guérin vaccine from Mycobacterium bovis bacillus is the only one used for immunization against tuberculosis. Unfortunately, it is effective only in newborns but not in adults; thus, efforts are still put to prepare an effective vaccine for immunization and treatment of adults. Malaria killed more than 1 million people in 2006, most of them were children. We still do not have any vaccine effective in prevention of malaria; nevertheless, some vaccine candidates appeared and are now in Phase I or Phase II trial.
