Silica-based cationic bilayers as immunoadjuvants.
BACKGROUND
Silica particles cationized by dioctadecyldimethylammonium bromide (DODAB) bilayer were previously described. This work shows the efficiency of these particulates for antigen adsorption and presentation to the immune system and proves the concept that silica-based cationic bilayers exhibit better performance than alum regarding colloid stability and cellular immune responses for vaccine design.


RESULTS
Firstly, the silica/DODAB assembly was characterized at 1 mM NaCl, pH 6.3 or 5 mM Tris.HCl, pH 7.4 and 0.1 mg/ml silica over a range of DODAB concentrations (0.001-1 mM) by means of dynamic light scattering for particle sizing and zeta-potential analysis. 0.05 mM DODAB is enough to produce cationic bilayer-covered particles with good colloid stability. Secondly, conditions for maximal adsorption of bovine serum albumin (BSA) or a recombinant, heat-shock protein from Mycobacterium leprae (18 kDa-hsp) onto DODAB-covered or onto bare silica were determined. At maximal antigen adsorption, cellular immune responses in vivo from delayed-type hypersensitivity reactions determined by foot-pad swelling tests (DTH) and cytokines analysis evidenced the superior performance of the silica/DODAB adjuvant as compared to alum or antigens alone whereas humoral response from IgG in serum was equal to the one elicited by alum as adjuvant.


CONCLUSIONS
Cationized silica is a biocompatible, inexpensive, easily prepared and possibly general immunoadjuvant for antigen presentation which displays higher colloid stability than alum, better performance regarding cellular immune responses and employs very low, micromolar doses of cationic and toxic synthetic lipid.
Lincopan
Nilton
N
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Caixa Postal 26077, São Paulo-SP, Brazil.
Santana
Mariana Ra
MR
Faquim-Mauro
Eliana
E
da Costa
Maria Helena B
MH
Carmona-Ribeiro
Ana M
AM
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000327:Adsorption; D000818:Animals; D000917:Antibody Formation; D017951:Antigen Presentation; D002412:Cations; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D008051:Lipid Bilayers / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000276:immunology*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D012822:Silicon Dioxide / Q000737:chemistry / Q000276:immunology*
D000276:Adjuvants, Immunologic; D002412:Cations; D016207:Cytokines; D008051:Lipid Bilayers; D000644:Quaternary Ammonium Compounds; C015831:dimethyldioctadecylammonium; D012710:Serum Albumin, Bovine; D012822:Silicon Dioxide