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Molecular adjuvants based on nonpyrogenic lipophilic derivatives of norAbuMDP/GMDP formulated in nanoliposomes: stimulation of innate and adaptive immunity
PT. Knotigová, D. Zyka, J. Mašek, A. Kovalová, M. Křupka, E. Bartheldyová, P. Kulich, Š. Koudelka, R. Lukáč, Z. Kauerová, A. Vacek, MS. Horynová, A. Kozubík, AD. Miller, L. Fekete, I. Kratochvílová, J. Ježek, M. Ledvina, M. Raška, J. Turánek,
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
NLK
ProQuest Central
from 1997-01-01 to 1 year ago
Medline Complete (EBSCOhost)
from 2010-01-01 to 1 year ago
Nursing & Allied Health Database (ProQuest)
from 1997-01-01 to 1 year ago
Health & Medicine (ProQuest)
from 1997-01-01 to 1 year ago
- MeSH
- Acetylmuramyl-Alanyl-Isoglutamine administration & dosage analogs & derivatives chemistry pharmacology therapeutic use MeSH
- Adaptive Immunity drug effects MeSH
- Adjuvants, Immunologic administration & dosage chemistry pharmacology therapeutic use MeSH
- Survival Analysis MeSH
- Antigens, Fungal immunology MeSH
- Radiation Injuries, Experimental immunology prevention & control MeSH
- Rabbits MeSH
- Liposomes MeSH
- Microscopy, Atomic Force MeSH
- Microscopy, Electron, Scanning MeSH
- Molecular Structure MeSH
- Mice, Inbred ICR MeSH
- Mice MeSH
- Nanoparticles MeSH
- Drug Carriers chemistry MeSH
- Immunity, Innate drug effects MeSH
- HSP90 Heat-Shock Proteins immunology MeSH
- Antibodies, Fungal blood MeSH
- Recombinant Proteins immunology MeSH
- Microscopy, Electron, Transmission MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
PURPOSE: The aim of this work was to demonstrate an immunostimulatory and adjuvant effect of new apyrogenic lipophilic derivatives of norAbuMDP and norAbuGMDP formulated in nanoliposomes. METHODS: Nanoliposomes and metallochelating nanoliposomes were prepared by lipid film hydration and extrusion methods. The structure of the liposomal formulation was studied by electron microscopy, AF microscopy, and dynamic light scattering. Sublethal and lethal γ-irradiation mice models were used to demonstrate stimulation of innate immune system. Recombinant Hsp90 antigen (Candida albicans) bound onto metallochelating nanoliposomes was used for immunisation of mice to demonstrate adjuvant activities of tested compounds. RESULTS: Safety and stimulation of innate and adaptive immunity were demonstrated on rabbits and mice. The liposomal formulation of norAbuMDP/GMDP was apyrogenic in rabbit test and lacking any side effect in vivo. Recovery of bone marrow after sublethal γ-irradiation as well as increased survival of mice after lethal irradiation was demonstrated. Enhancement of specific immune response was demonstrated for some derivatives incorporated in metallochelating nanoliposomes with recombinant Hsp90 protein antigen. CONCLUSIONS: Liposomal formulations of new lipophilic derivatives of norAbuMDP/GMDP proved themselves as promising adjuvants for recombinant vaccines as well as immunomodulators for stimulation of innate immunity and bone-marrow recovery after chemo/radio therapy of cancer.
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- $a PURPOSE: The aim of this work was to demonstrate an immunostimulatory and adjuvant effect of new apyrogenic lipophilic derivatives of norAbuMDP and norAbuGMDP formulated in nanoliposomes. METHODS: Nanoliposomes and metallochelating nanoliposomes were prepared by lipid film hydration and extrusion methods. The structure of the liposomal formulation was studied by electron microscopy, AF microscopy, and dynamic light scattering. Sublethal and lethal γ-irradiation mice models were used to demonstrate stimulation of innate immune system. Recombinant Hsp90 antigen (Candida albicans) bound onto metallochelating nanoliposomes was used for immunisation of mice to demonstrate adjuvant activities of tested compounds. RESULTS: Safety and stimulation of innate and adaptive immunity were demonstrated on rabbits and mice. The liposomal formulation of norAbuMDP/GMDP was apyrogenic in rabbit test and lacking any side effect in vivo. Recovery of bone marrow after sublethal γ-irradiation as well as increased survival of mice after lethal irradiation was demonstrated. Enhancement of specific immune response was demonstrated for some derivatives incorporated in metallochelating nanoliposomes with recombinant Hsp90 protein antigen. CONCLUSIONS: Liposomal formulations of new lipophilic derivatives of norAbuMDP/GMDP proved themselves as promising adjuvants for recombinant vaccines as well as immunomodulators for stimulation of innate immunity and bone-marrow recovery after chemo/radio therapy of cancer.
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