Metallochelating liposomes with associated lipophilised norAbuMDP as biocompatible platform for construction of vaccines with recombinant His-tagged antigens: Preparation, structural study and immune response towards rHsp90

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Authors

MAŠEK Josef BARTHELDYOVÁ Eliška TURÁNEK KNÖTIGOVÁ Pavlína ŠKRABALOVÁ Michaela KORVASOVÁ Zina PLOCKOVÁ Jana KOUDELKA Štěpán ŠKODOVÁ Petra KULICH Pavel KŘUPKA Michal ZACHOVÁ Kateřina CZERNEKOVÁ Lýdie HORYNOVÁ Milada KRATOCHVÍLOVÁ Irena MILLER Andrew D. ZÝKA Daniel MICHÁLEK Jaroslav VRBKOVÁ Jana ŠEBELA Marek LEDVINA Miroslav RAŠKA Milan TURÁNEK Jaroslav

Year of publication 2011
Type Article in Periodical
Magazine / Source JOURNAL OF CONTROLLED RELEASE
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1016/j.jconrel.2011.01.016
Field Pharmacology and pharmaceutical chemistry
Keywords Recombinant vaccine; Liposome; Heat shock; protein; Hsp90; Muramyl; dipeptide; Candida albicans
Description Hsp90-CA is present in cell wall of Candida pseudohyphae or hyphae-typical pathogenic morphotype for both systemic and mucosal Candida infections. Heat shock protein from Candida albicans (hsp90-CA) is an important target for protective antibodies during disseminated candidiasis of experimental mice and human. His-tagged protein rHsp90 was prepared and used as the antigen for preparation of experimental recombinant liposomal vaccine. Nickel-chelating liposomes (the size around 100 nm) were prepared from the mixture of egg phosphatidyl choline and nickel-chelating lipid DOGS-NTA-Ni (molar ratio 95:5%) by hydration of lipid film and extrusion methods. New non-pyrogenic hydrophobised derivative of MDP (C18-O-6-norAbuMDP) was incorporated into liposomes as adjuvans. rHsp90 was attached onto the surface of metallochelating liposomes by metallochelating bond and the structure of these proteoliposomes was studied by dynamic light scattering, AF microscopy, TEM and GPC. The liposomes with surface-exposed C18-O-6-norAbuMDP were well recognised and phagocyted by human dendritic cells in vitro. In vivo the immune response towards this experimental vaccine applied in mice (i.d.) demonstrated both TH1 and TH2 response comparable to FCA, but without any side effects. Metallochelating liposomes with lipophilic derivatives of muramyl dipeptide represent a new biocompatible platform for construction of experimental recombinant vaccines and drug-targeting systems.
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