title: Protective effect of antigen delivery using monoolein-based liposomes in experimental hematogenously disseminated candidiasis.
abstract: We evaluated the potential of a liposomal antigen delivery system (ADS) containing Candida albicans cell wall surface proteins (CWSP) in mediating protection against systemic candidiasis. Treatment of bone-marrow-derived dendritic cells with CWSP-loaded dioctadecyldimethylammonium bromide:monoolein (DODAB:MO) liposomes enhanced and prolonged their activation comparatively to free antigen, indicating that liposome-entrapped CWSP were released more sustainable. Therefore, we immunized mice with CWSP either in a free form or loaded into two different DODAB:MO liposome formulations, respectively designated as ADS1 and ADS2, prior to intravenous C. albicans infection. Immunization with ADS1, but not with ADS2, conferred significant protection to infected mice, comparatively to immunization with CWSP or empty liposomes as control. ADS1-immunized mice presented significantly higher serum levels of C. albicans-specific antibodies that enhanced phagocytosis of this fungus. In these mice, a mixed cytokine production profile was observed encompassing IFN-γ, IL-4, IL-17A and IL-10. Nevertheless, only production of IL-4, IL-17 and IL-10 was higher than in controls. In this study we demonstrated that DODAB:MO liposomes enhance the immunogenicity of C. albicans antigens and host protection in a murine model of systemic candidiasis. Therefore, this liposomal adjuvant could be a promising candidate to assess in vaccination against this pathogenic fungus.
  
  
  
  This work describes the immunomodulation capacity of the previously validated antigen delivery system (ADS) composed by dioctadecyldimethylammonium bromide (DODAB) and monoolein (MO) lipids incorporating the cell wall surface proteins (CWSP) from C. albicans. Here, we not only present the ability of this system in facilitating antigen uptake by DCs in vitro, but also that this system induces higher levels of pro-inflammatory cytokines and opsonizing specific IgG antibodies in serum of mice immunized subcutaneously. We show that the ADS are efficient nanocarrier and modulate the immune response against intravenous C. albicans infection favoring mouse protection. In sum, we show that the incorporation of C. albicans antigens in DODAB:MO nanocarries are a promising vaccine strategy against C. albicans fungal infection.
authors.affiliation: Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, 4710-057 Braga, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Carneiro
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4150-180 Porto, Portugal; IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Correia
authors.affiliation: Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, 4710-057 Braga, Portugal.
authors.forename: Tânia
authors.initials: T
authors.lastname: Lima
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4150-180 Porto, Portugal; IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal; Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Rua de Jorge Viterbo Ferreira n.° 228, 4050-313 Porto, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Vilanova
authors.affiliation: Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, 4710-057 Braga, Portugal.
authors.forename: Célia
authors.initials: C
authors.lastname: Pais
authors.affiliation: Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, 4710-057 Braga, Portugal; NanoDelivery I&D in Biotecnology, Biology Department, Campus of Gualtar, 4710-057 Braga, Portugal.
authors.forename: Andreia C
authors.initials: AC
authors.lastname: Gomes
authors.affiliation: Centre of Physics (CFUM) University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal; NanoDelivery I&D in Biotecnology, Biology Department, Campus of Gualtar, 4710-057 Braga, Portugal.
authors.forename: M Elisabete C D
authors.initials: MECD
authors.lastname: Real Oliveira
authors.affiliation: Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, 4710-057 Braga, Portugal. Electronic address: psampaio@bio.uminho.pt.
authors.forename: Paula
authors.initials: P
authors.lastname: Sampaio
mesh_terms: D000818:Animals; D000946:Antigens, Fungal / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D002176:Candida albicans / Q000276:immunology*; D058365:Candidiasis, Invasive / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D005656:Fungal Proteins / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D005657:Fungal Vaccines / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D005989:Glycerides / Q000737:chemistry / Q000494:pharmacology; D007114:Immunization / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000946:Antigens, Fungal; D005656:Fungal Proteins; D005657:Fungal Vaccines; D005989:Glycerides; D000644:Quaternary Ammonium Compounds; C015831:dimethyldioctadecylammonium; C005953:monoolein
keywords: Antigen delivery systems; Candida albicans proteins; DODAB:MO liposomes; Dendritic cells; Humoral and cellular immune responses; Nanoparticles