Liposome-formulated interleukin-2 as an adjuvant of recombinant HSV glycoprotein gD for the treatment of recurrent genital HSV-2 in guinea-pigs.
The use of interleukin-2 (IL-2) as an adjuvant to enhance an antigen-induced immunotherapeutic effect was investigated using guinea-pigs with established HSV-2 infection. Animals treated with four weekly doses of liposome-formulated IL-2 (2.7 x 10(5) U kg-1 dose) overlapping two biweekly doses of an HSV-recombinant glycoprotein D (rgD) treatment demonstrated approximately 70% reduction in HSV-2 recurrent disease compared with placebo (p less than 0.005). Combination therapy rgD plus liposome-formulated IL-2 exhibited approximately 30% greater therapeutic effect than either agent alone (p less than 0.05). Liposome formulation of IL-2 was essential to elicit the adjuvant effect. Identical biweekly dosing or more frequent daily dosing of soluble IL-2 did not produce additional therapeutic effects, suggesting the role of liposome targeting to lymph nodes. Although rgD plus liposome-formulated IL-2 induced a marginal early antibody response to rgD, there was no significant increase in overall antibody response. Combination therapy increased the frequency of minimally positive HSV lymphoproliferative response.
Ho
R J
RJ
Department of Medicine, Stanford University School of Medicine, CA 94305.
Burke
R L
RL
Merigan
T C
TC
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000628:therapy*; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000276:immunology; D008081:Liposomes / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage; D012008:Recurrence; D014759:Viral Envelope Proteins / Q000008:administration & dosage*
D000914:Antibodies, Viral; D004337:Drug Carriers; D007376:Interleukin-2; D008081:Liposomes; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins