Liposomes represent a perfect tool to enhance the cross-presentation effectivity of viral HIV-1 p24 protein fused with heat shock protein 70

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F20%3AN0000207" target="_blank" >RIV/00027162:_____/20:N0000207 - isvavai.cz</a>

Výsledek na webu

<a href="https://plan.core-apps.com/aai2020/abstract/11705440-77fc-4ae2-afb3-60f5b4c4d560" target="_blank" >https://plan.core-apps.com/aai2020/abstract/11705440-77fc-4ae2-afb3-60f5b4c4d560</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Liposomes represent a perfect tool to enhance the cross-presentation effectivity of viral HIV-1 p24 protein fused with heat shock protein 70

Popis výsledku v původním jazyce

Current approaches focusing on anti-viral and anti-tumor vaccines developement tend to induce strong CD4 T cell response leading in antibodies production and simultaneously, efficient CD8 T cell activation responsible for cytotoxic elimination of infected cells. The p24 protein from HIV-1 virus is a relatively conserved but poorly immunogenic protein. Its fusion with host heat shock protein 70 (hsp70) enhanced the immune response to p24 including cross-presentation on MHC I molecules, despite the recognition by antigen presenting cells as an exogenous antigen. Cross-presentation efficacy and immune response was supported by binding this construct to liposomes containing aminooxy lipids allowing further modification by click chemistry. Hsp70-p24 was bound to liposome surface and used in cDC1 cell line (DCs from murine spleen) and mice vaccination model. Activation markers, MHCI expression, apoptosis assay and proliferation efficacy was analyzed. Expression of DC cell-surface activation markers CD40, CD86 and also MHC I was increased in hsp70-p24 pulsed cells as much as LPS, but when antigens coupled to liposome expression was significantly higher. None of the constructs activated CD86 expression as much as the LPS. Studies on hepatocytes transfected by hsp70-p24 encoding plasmid DNA showed increased death of hepatocytes co-cultivated with splenocytes from mice vaccinated by hsp70-p24-liposome in comparison to hsp70-p24 alone. Activation markers on CD8 T cells from vaccinated mice were enhanced after co-cultivation with hsp70-p24-liposome pulsed cDC1 cells or bone marrow derived dendritic cells. All these results clearly show that coupling of antigen with liposomes leads to effective CD4 and also CD8 T cell activation.

Název v anglickém jazyce

Liposomes represent a perfect tool to enhance the cross-presentation effectivity of viral HIV-1 p24 protein fused with heat shock protein 70

Popis výsledku anglicky

Current approaches focusing on anti-viral and anti-tumor vaccines developement tend to induce strong CD4 T cell response leading in antibodies production and simultaneously, efficient CD8 T cell activation responsible for cytotoxic elimination of infected cells. The p24 protein from HIV-1 virus is a relatively conserved but poorly immunogenic protein. Its fusion with host heat shock protein 70 (hsp70) enhanced the immune response to p24 including cross-presentation on MHC I molecules, despite the recognition by antigen presenting cells as an exogenous antigen. Cross-presentation efficacy and immune response was supported by binding this construct to liposomes containing aminooxy lipids allowing further modification by click chemistry. Hsp70-p24 was bound to liposome surface and used in cDC1 cell line (DCs from murine spleen) and mice vaccination model. Activation markers, MHCI expression, apoptosis assay and proliferation efficacy was analyzed. Expression of DC cell-surface activation markers CD40, CD86 and also MHC I was increased in hsp70-p24 pulsed cells as much as LPS, but when antigens coupled to liposome expression was significantly higher. None of the constructs activated CD86 expression as much as the LPS. Studies on hepatocytes transfected by hsp70-p24 encoding plasmid DNA showed increased death of hepatocytes co-cultivated with splenocytes from mice vaccinated by hsp70-p24-liposome in comparison to hsp70-p24 alone. Activation markers on CD8 T cells from vaccinated mice were enhanced after co-cultivation with hsp70-p24-liposome pulsed cDC1 cells or bone marrow derived dendritic cells. All these results clearly show that coupling of antigen with liposomes leads to effective CD4 and also CD8 T cell activation.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/EF15_003%2F0000495" target="_blank" >EF15_003/0000495: FIT (Farmakologie, Imunoterapie, nanoToxikologie)</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů