Endotoxin-minimized HIV-1 p24 fused to murine hsp70 activates dendritic cells, facilitates endocytosis and p24-specific Th1 response in mice
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26021827
DOI
10.1016/j.imlet.2015.05.010
PII: S0165-2478(15)00086-3
Knihovny.cz E-zdroje
- Klíčová slova
- HIV, HIV-1 protein p24, Heat shock protein, Vaccine,
- MeSH
- antigeny virové imunologie MeSH
- CD8-pozitivní T-lymfocyty imunologie MeSH
- dendritické buňky imunologie MeSH
- endocytóza imunologie MeSH
- endotoxiny imunologie MeSH
- HIV korový protein p24 imunologie metabolismus MeSH
- imunizace MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- nepřímá aktivace imunologie MeSH
- proteiny tepelného šoku HSP70 imunologie metabolismus MeSH
- rekombinantní fúzní proteiny imunologie MeSH
- Th1 buňky imunologie MeSH
- vakcíny proti AIDS imunologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigeny virové MeSH
- endotoxiny MeSH
- HIV korový protein p24 MeSH
- proteiny tepelného šoku HSP70 MeSH
- rekombinantní fúzní proteiny MeSH
- vakcíny proti AIDS MeSH
Heat shock proteins hsp70 and gp96 have been confirmed as adjuvants enabling induction of cell- and antibody-mediated immunity specific to associated protein or peptide antigens due to the activation of naive dendritic cells and supporting cross-presentation of associated antigen. An efficacious vaccine preventing HIV-1 infection should induce (1) antibodies neutralizing HIV-1 Env protein, preventing virus spreading and (2) CD4(+) Th1 and CD8(+) T cells specific to viral proteins, especially gag p24, important for elimination of HIV-1 infected cells. As p24 is relatively poorly recognized by dendritic cells, its targeting to DC is important for enhancement of vaccine efficacy. In this study, a p24 protein fused to the C- or N-terminus of murine hsp70 was produced as a recombinant protein and administered without any adjuvant to experimental BALB/c mice. Consequently, p24-specific cellular and humoral immune responses were measured. To minimize the effect of bacterial endotoxin, each protein was subjected to a repeated endotoxin phase extraction until each preparation contained less than 2.5 endotoxin unit (EU) per mg of antigen. In addition, endocytosis of p24 fused to hsp70 by dendritic cells and their activation were characterized. The fusion to hsp70 protein enhanced endocytosis of p24 as well as activation of dendritic cells in vitro. After immunization of mice, hsp70-p24 fusion protein induced the strongest p24-specific CD4(+) and CD8(+) T cells (IFN-γ production) and humoral (IgG2b) responses corresponding to Th1 type dominance, whereas p24-hsp70 or p24 itself induced weaker responses.
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