An Increased Adjuvanticity of Liposomes by the Inclusion of Phosphatidylserine in Immunization with Surface-Coupled Liposomal Antigen

Abstract

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.

Design considerations for liposomal vaccines: Influence of formulation parameters on antibody and cell-mediated immune responses to liposome associated antigens

“…PS is recognized by a specific receptor on macrophages as part of the process of clearance of apoptotic cells, leading to production of TGF-β and induction of an anti-inflammatory state in macrophages [158, 159]. Nonetheless, in some cases PS exhibited a beneficial adjuvant effect; in one instance PS liposomes elicited a higher OVA-specific serum IgG titer against surface-associated OVA when compared an analogous PC-containing formulation [160]. Lysophospholipids such as lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are also important regulators of innate and adaptive immunity [161, 162].…”

The Use of Synthetic Carriers in Malaria Vaccine Design

“…For instance, incorporation of PEG into the lipid surface enhances the distribution time in blood [ 133 ]. Antigen is commonly encapsulated in the aqueous center of the liposome, with surface conjugation used to a lesser degree [ 134 ]. Advantages include the ability to incorporate both hydrophilic and hydrophobic antigens, and the systems’ biodegradability [ 107 ].…”

Therapeutic Liposomal Vaccines for Dendritic Cell Activation or Tolerance

“…In the tolerogenic field, liposomes containing the negatively charged lipid, phosphatidylserine (PS) gained considerable attention ( 22 , 60 , 61 ). The most prominent theory for a tolerogenic adjuvant effect of PS containing particles puts forth the notion that such particles resemble apoptotic bodies, thereby silencing DC maturation upon their encounter.…”