title: Molecular adjuvants based on nonpyrogenic lipophilic derivatives of norAbuMDP/GMDP formulated in nanoliposomes: stimulation of innate and adaptive immunity.
abstract: OBJECTIVE
  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.
authors: Department of Pharmacology and Immunotherapy, Veterinary Research Institute, Hudcova 70, 620 00, Brno, Czech Republic.
authors: Pavlína Turánek
authors: PT
authors: Knotigová
authors: Daniel
authors: D
authors: Zyka
authors: Josef
authors: J
authors: Mašek
authors: Anna
authors: A
authors: Kovalová
authors: Michal
authors: M
authors: Křupka
authors: Eliška
authors: E
authors: Bartheldyová
authors: Pavel
authors: P
authors: Kulich
authors: Štěpán
authors: Š
authors: Koudelka
authors: Róbert
authors: R
authors: Lukáč
authors: Zuzana
authors: Z
authors: Kauerová
authors: Antonín
authors: A
authors: Vacek
authors: Milada Stuchlová
authors: MS
authors: Horynová
authors: Alois
authors: A
authors: Kozubík
authors: Andrew D
authors: AD
authors: Miller
authors: Ladislav
authors: L
authors: Fekete
authors: Irena
authors: I
authors: Kratochvílová
authors: Jan
authors: J
authors: Ježek
authors: Miroslav
authors: M
authors: Ledvina
authors: Milan
authors: M
authors: Raška
authors: Jaroslav
authors: J
authors: Turánek
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D056704:Adaptive Immunity / Q000187:drug effects*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood; D000946:Antigens, Fungal / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects*; D008081:Liposomes; D051379:Mice; D008813:Mice, Inbred ICR; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D053758:Nanoparticles; D011817:Rabbits; D011833:Radiation Injuries, Experimental / Q000276:immunology / Q000517:prevention & control; D011994:Recombinant Proteins / Q000276:immunology; D016019:Survival Analysis
chemical_list: D000276:Adjuvants, Immunologic; D000908:Antibodies, Fungal; D000946:Antigens, Fungal; D004337:Drug Carriers; D018841:HSP90 Heat-Shock Proteins; D008081:Liposomes; D011994:Recombinant Proteins; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C037058:N-acetylmuramyl-aminobutyryl-isoglutamine; C063429:glucosaminylmuramyl-2-alanine-D-isoglutamine
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