An increased adjuvanticity of liposomes by the inclusion of phosphatidylserine in immunization with surface-coupled liposomal antigen.
BACKGROUND
Exposure of phosphatidylserine (PS) on apoptotic cells is known to result in the enhanced recognition of apoptotic cells by phagocytes. By the inclusion of PS in the lipid component of liposomes, increased liposome immune adjuvant activity was expected.


METHODS
In the present study, two different liposome preparations containing either PS, i.e. PS-liposome, or phosphatidylcholine (PC), i.e. PC-liposome, were made, and macrophage recognition, processing, and antigen presentation of surface-coupled liposomal antigen were compared.


RESULTS
When ovalbumin-liposome conjugates were added to a culture of macrophages, enhanced recognition and processing of ovalbumin by the macrophages were observed by the inclusion of PS in the liposomes. The results correlated well with those regarding macrophage antigen presentation of liposome-coupled ovalbumin. Furthermore, in vivo immunization in mice with ovalbumin-liposome conjugates made with PS-liposomes induced a significantly higher level of anti-ovalbumin IgG antibody production than was induced by ovalbumin-liposome conjugates made with PC-liposomes. IgE-selective unresponsiveness was induced by ovalbumin-liposome conjugates regardless of the lipid components of liposomes.


CONCLUSIONS
These results suggest that the inclusion of PS in liposomes enhances recognition and processing of surface-coupled liposomal antigen by macrophages, and increases liposome immune adjuvant activity.
Mori
Masahito
M
Drug Delivery System Development Division, Nippon Oil and Fat Corporation, Tokyo, Japan.
Nishida
Mitsuhiro
M
Maekawa
Naoya
N
Yamamura
Hiroyuki
H
Tanaka
Yuriko
Y
Kasai
Michiyuki
M
Taneichi
Maiko
M
Uchida
Tetsuya
T
D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D000954:Antigens, Surface / Q000276:immunology; D015195:Drug Design; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry* / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology*; D010587:Phagocytosis; D010713:Phosphatidylcholines / Q000737:chemistry / Q000494:pharmacology; D010718:Phosphatidylserines / Q000737:chemistry / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
D000276:Adjuvants, Immunologic; D000954:Antigens, Surface; D007074:Immunoglobulin G; D008055:Lipids; D008081:Liposomes; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D010047:Ovalbumin