Interactions between cationic liposomes and an antigenic protein: the physical chemistry of the immunoadjuvant action.
The 18 kDa antigenic protein from Mycobacterium leprae (P) or its N-acyl derivative (AP) was incorporated in dioctadecyldimethylammonium bromide (DODAB) liposomes in water or in phosphate-buffered saline (PBS). In water, 100% P incorporation in liposomes contrasts with 65% in PBS. There is 75-80% AP incorporation to liposomes in water against 55-65% in PBS, showing that attachment of hydrophobic residues to the protein, instead of increasing, further decreases incorporation to the liposomes. From protein adsorption on latex, P affinity is larger than AP affinity for the latex surface whereas limiting adsorption for AP is much larger than that obtained for P, possibly due to AP aggregation in solution. P-induced rupture of liposomes containing [14C]sucrose was evaluated from dialysis of protein/liposomes mixtures. In water, P incorporation to the liposomes causes leakage of radioactive contents contrasting with the absence of leakage for P incorporation in PBS. Immunization tests for delayed type hypersensitivity indicate a enhancement of cell-mediated immunological response towards P/DODAB complexes that is not obtained for the isolated protein. Absence of leakage for P in PBS is associated with a P "lying-over" on the liposome and optimization of protein presentation to the immunological system.
Tsuruta
L R
LR
Departamento de Bioquímica, Instituto de Quimica, S. Paulo, SP, Brazil.
Quintilio
W
W
Costa
M H
MH
Carmona-Ribeiro
A M
AM
D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000327:Adsorption; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000276:immunology; D002412:Cations / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005260:Female; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000276:immunology; D006968:Hypersensitivity, Delayed; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009166:Mycobacterium leprae / Q000276:immunology*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D013395:Sucrose / Q000737:chemistry; D014867:Water
D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D002412:Cations; D006360:Heat-Shock Proteins; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; D011994:Recombinant Proteins; C081475:hsp18 protein, bacteria; D014867:Water; C015831:dimethyldioctadecylammonium; D013395:Sucrose