Disposition of antigen-presenting liposomes in vivo: effect on presentation of herpes simplex virus antigen rgD.
Antigen-presenting liposomes (APLs) containing a lipophilic derivative of muramyl tripeptide (MTP-PE) have previously been shown to enhance the immunotherapeutic effects mediated by HSV recombinant protein gD (rgD) after HSV type 2 infection is established. In this study, both the in vivo disposition of rgD and the immunological activity of in vivo-delivered rgD were determined. Following intravenous administration, most of the liposome-encapsulated rgD accumulated rapidly, mainly in the spleen, while most of the soluble rgD was quickly eliminated through the kidney. We have compared the T-cell stimulatory effects of macrophages, B cells and dendritic cells from the spleens of animals treated with rgD in vivo. Of these antigen-presenting cells, only adherent macrophages, isolated from the spleens of animals treated with rgD encapsulated in APLs for 90 minutes, were capable of stimulating HSV-sensitized autologous T and B cells. Additional in vitro exposure of macrophages to rgD was not required. In contrast, spleen macrophages from HSV-sensitized animals exposed to either empty liposomes or free rgD did not exhibit such immune responses, indicating that the immunobiological effect of the rgD delivered in APLs is antigen- and carrier-specific. The enhanced delivery of antigen to spleen cells, coupled with MTP-PE immunostimulatory activity, may be the key factors for the enhanced therapeutic effects observed in treating HSV-2 disease in guinea pigs. This approach will be useful to enhance the induction of secondary immune responses in postinfection vaccination schemes.
Ho
R J
RJ
Department of Pharmaceutics, University of Washington School of Pharmacy, Seattle 98195.
Burke
R L
RL
Merigan
T C
TC
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology; D006224:Cricetinae; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology / Q000517:prevention & control; D018258:Herpesvirus 2, Human / Q000276:immunology*; D008081:Liposomes; D008264:Macrophages / Q000276:immunology; D010714:Phosphatidylethanolamines; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism*
D000956:Antigens, Viral; D008081:Liposomes; D010714:Phosphatidylethanolamines; D014759:Viral Envelope Proteins; C040570:glycoprotein D-herpes simplex virus type 2; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine