CAF01 liposomes as a mucosal vaccine adjuvant: In vitro and in vivo investigations.
Mucosal administration of vaccines has many advantages compared to parenteral vaccination. Needle-free mucosal vaccination would be easily applicable, target the vaccine to the entry point of many pathogens, and reduce the risk of infection with other pathogens during vaccination as compared to invasive methods. CAF01 is a novel liposome-based vaccine adjuvant with remarkable immunostimulatory activity. The potential of CAF01 liposomes as adjuvant for mucosal vaccines was investigated using the Calu-3 epithelial cell culture in vitro model. Thus, the mucosal permeability of the antigen as well as the epithelial integrity and the metabolic activity of the well-differentiated cells were investigated after exposure to CAF01. Finally, the adjuvant was tested for nasal administration in mice, combined with an influenza vaccine. The results suggest that CAF01 enhanced transport of antigen through the mucus layer on Calu-3 cells, increasing the concentration of antigen in the cell layer, as well as the transport across the epithelial cells. Furthermore CAF01 was well tolerated by the Calu-3 cells and the in vivo studies demonstrated increased cell-mediated immunity (CMI) as well as humoral immune responses in mice after nasal application of the influenza vaccine when combined with CAF01. CAF01 is thus a promising adjuvant for mucosal delivery.
Christensen
Dennis
D
Statens Serum Institut, Department of Infectious Disease Immunology, Vaccine Delivery & Formulation, Artillerivej 5, DK-2300 Copenhagen S, Denmark. den@ssi.dk
Foged
Camilla
C
Rosenkrands
Ida
I
Lundberg
Carina Vingsbo
CV
Andersen
Peter
P
Agger
Else Marie
EM
Nielsen
Hanne Mørck
HM
D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D017097:Electric Impedance; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006017:Glycolipids / Q000737:chemistry; D018928:Immunity, Mucosal / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry* / Q000494:pharmacology; D008353:Mannitol / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014612:Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology
D000276:Adjuvants, Immunologic; D006017:Glycolipids; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; D014612:Vaccines; D015164:Vaccines, Inactivated; C507803:trehalose 6,6'-dibehenate; C478242:vaxigrip; C015831:dimethyldioctadecylammonium; D008353:Mannitol; D007371:Interferon-gamma; D010047:Ovalbumin