Reduction of recurrent HSV disease using imiquimod alone or combined with a glycoprotein vaccine.
The aim of this study is to evaluate the effects of an immune modulator, imiquimod, given alone or in combination with an HSV vaccine on HSV immune responses and as immunotherapy of a genital recurrence model. After recovery from primary genital HSV infection, animals were randomized to placebo, 21 days of imiquimod plus a placebo vaccine, or 21 days of imiquimod plus an HSV-2 glycoprotein vaccine. Placebo or HSV vaccine was given in the footpad on days 16 and 37 after HSV-2 genital inoculation. Daily imiquimod or placebo was given subcutaneously in the shoulder on days 16 through 37. Genital recurrences were monitored and HSV specific NK activity, IL-2 response and ELISA antibody were assayed. For the entire 15 week observation period, imiquimod alone reduced recurrences 62.6%, while addition of HSV vaccine to imiquimod reduced recurrences 80.6% compared to placebo/placebo. The duration of significant recurrence reduction was more notable with the addition of vaccine. Imiquimod alone significantly reduced the weekly HSV recurrent disease in the first 10 weeks (53-94% reduction, mean 75.9%), as did imiquimod plus HSV-vaccine (71-98% reduction, mean 89.5%). In weeks 10-15, imiquimod alone reduced recurrences significantly only in week 10 (20-53% reduction, mean 33%), whereas the addition of vaccine extended the significant recurrence reduction to 14 weeks (44-71% reduction, mean 56.8%). The recurrence reduction is correlated to an increased HSV-induced in vitro IL-2 response and NK activity against HSV targets in treated groups. Both imiquimod and the imiquimod/vaccine combination significantly reduced genital HSV recurrences, but the combination extended the duration and extent of protection for recurrences compared to imiquimod alone. Enhanced HSV specific immune responses correlated to the protection.
Harrison
C J
CJ
Creighton University, Division of Pediatric Infectious Diseases, 2500 California Plaza, Criss II-Room 409, Omaha, NE 68178, USA. charriso@creighton.edu
Miller
R L
RL
Bernstein
D I
DI
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000634:Aminoquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000821:virology; D022301:Herpes Simplex Virus Vaccines / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000187:drug effects / Q000276:immunology*; D000077271:Imiquimod; D007279:Injections, Subcutaneous; D007369:Interferon Inducers / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology
D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000914:Antibodies, Viral; D000956:Antigens, Viral; D006023:Glycoproteins; D022301:Herpes Simplex Virus Vaccines; D007369:Interferon Inducers; D007376:Interleukin-2; D014759:Viral Envelope Proteins; D000077271:Imiquimod