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.