Physical and biological characterization of antigen presenting liposome formulations: relative efficacy for the treatment of recurrent genital HSV-2 in guinea pigs.
Antigen presenting liposomes (APLs) containing both liposome encapsulated (44%) and free (56%) recombinant glycoprotein D of herpes simplex virus type-2 (rgD-2) were characterized with respect to the interaction of the antigen with the lipid bilayer and the biological activities provided by each form of rgD-2. We found that free rgD-2 added externally to empty liposomes exhibited some biological activities both in vitro and in vivo, although we could not detect any significant adsorption and/or insertion of this form of rgD-2 into the lipid bilayer. Compared to APLs containing both forms of rgD-2, purified liposomes containing only encapsulated rgD-2 gave only 50% of the relative activity in vitro as measured by their ability to stimulate rgD-2 specific lymphocyte proliferation, and 67% of the relative activity in vivo as measured by their immunotherapeutic effect on recurrent genital HSV-2 disease in guinea pigs (P less than 0.05). These data indicate that while liposome encapsulated rgD-2 is essential for the elicitation of immunogenic responses, the free soluble rgD-2 in the APL formulation also acts in concert to generate an optimum immunotherapeutic efficacy.
Ho
R J
RJ
Department of Medicine, Stanford University School of Medicine, CA 94305.
Burke
R L
RL
Merigan
T C
TC
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002214:Capsules; D002462:Cell Membrane / Q000276:immunology; D005260:Female; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D007108:Immune Tolerance; D066298:In Vitro Techniques; D008081:Liposomes; D008214:Lymphocytes / Q000276:immunology / Q000382:microbiology; D011994:Recombinant Proteins / Q000008:administration & dosage; D012008:Recurrence; D014759:Viral Envelope Proteins / Q000008:administration & dosage* / Q000494:pharmacology
D000956:Antigens, Viral; D000998:Antiviral Agents; D002214:Capsules; D008081:Liposomes; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C040570:glycoprotein D-herpes simplex virus type 2