Disposition of antigen-presenting liposomes in vivo: effect on presentation of herpes simplex virus antigen rgD.

ABSTRACT

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.