Augmentation of alphavirus vector-induced human papilloma virus-specific immune and anti-tumour responses by co-expression of interleukin-12.
To enhance the efficacy of a therapeutic immunisation strategy against human papillomavirus-induced cervical cancer we evaluated the adjuvant effect of interleukin-12 (IL12) expressed by a Semliki Forest virus vector (SFV) in mice. Depending on the dose and schedule, SFV-IL12 stimulated antigen-specific CTL responses elicited upon immunisation with recombinant SFV expressing HPV16-E6E7 (SFVeE6,7). SFVeE6,7-CTL and anti-tumour activity were enhanced by a low dose of SFV-IL12 to the prime immunisation. Using higher dosages these activities were reduced. Addition of SFV-IL12 to the booster immunisation further reduced the efficacy of the SFVeE6,7 immunisation. In transgenic mice, tolerant for HPV16-E6E7, SFV-IL12 also stimulated SFVeE6,7-induced CTL responses. In conclusion, SFV-IL12 can enhance antigen-specific immune responses. Yet, prudence is called for when considering co-administration of SFV-IL12 to a vaccine, as the enhancement of cell-mediated immune responses greatly depends on dosage and schedule.
Riezebos-Brilman
Annelies
A
Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands.
Regts
Joke
J
Chen
Margaret
M
Wilschut
Jan
J
Daemen
Toos
T
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D006224:Cricetinae; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007117:Immunization, Secondary; D018664:Interleukin-12 / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009369:Neoplasms / Q000473:pathology / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000276:immunology*; D012672:Semliki forest virus / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D053918:Papillomavirus Vaccines; D018664:Interleukin-12