Immunotherapy of acute and recurrent herpes simplex virus type 2 infection with an adjuvant-free form of recombinant glycoprotein D-interleukin-2 fusion protein.
Previous studies demonstrated that the adjuvant-free form of a fusion protein consisting of a truncated herpes simplex virus type 1 (HSV-1) glycoprotein D and human interleukin-2 (tgD-IL-2) elicited superior protective immunity in mice. In this study, the immunotherapeutic efficacy of tgD-IL-2 against vaginal HSV-2 infection was investigated using a guinea pig model. Footpad injections of tgD-IL-2 (12.5 micrograms/dose) after the onset of primary lesions strongly suppressed recurrence in the chronic phase of infection; consequently, the number of days with lesions was reduced 65%. Continuous medication with 100 mg/kg/day acyclovir for 5 days failed to suppress recurrent infection. In a UV radiation-induced recurrence model, prophylactic tgD-IL-2 significantly suppressed both duration and severity of disease. A single injection of tgD-IL-2 plus acyclovir produced an additive effect on the suppression of the disease in the acute phase. These results suggest that tgD-IL-2 is a promising immunotherapeutic agent against HSV-2 genital infections.
Nakao
M
M
Pharmaceutical Research and Discovery Research Divisions, Takeda Chemical Industries, Osaka, Japan.
Hazama
M
M
Mayumi-Aono
A
A
Hinuma
S
S
Fujisawa
Y
Y
D000208:Acute Disease; D000212:Acyclovir / Q000627:therapeutic use; D000818:Animals; D017024:Chemotherapy, Adjuvant; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000628:therapy*; D018258:Herpesvirus 2, Human / Q000276:immunology* / Q000502:physiology / Q000528:radiation effects; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012008:Recurrence; D014466:Ultraviolet Rays; D014621:Vagina / Q000382:microbiology; D014759:Viral Envelope Proteins / Q000627:therapeutic use*; D014779:Virus Replication; D017201:Virus Shedding
D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; C040570:glycoprotein D-herpes simplex virus type 2; D000212:Acyclovir