Modulation of cellular and humoral immune responses to a multiepitopic HIV-1 DNA vaccine by interleukin-18 DNA immunization/viral protein boost

In this study, the impact of Th1-inducing cytokine gene co-delivery and ant igen boosting on humoral and cellular responses induced by multiepitopic DN A immunization in mice have been investigated. Intramuscular injection of m ixed DNA constructs encoding for HIV-1 Gag, Tat and Nef proteins, co-admini stered with the DNA encoding for interleukin-18 (IL-18) have been used. The effect of boosting with the recombinant proteins was also evaluated on the outcome of the responses in DNA-primed mice. It was demonstrated that at l east two DNA immunizations were necessary to generate virus specific Th-l r esponses detected by the presence of cytotoxic T lymphocyte (CTL) and by th e secretion of IL-2 and IFN-gamma, but not IL-4 and IL-10, in antigen-stimu lated splenocyte cultures. Interestingly, co-delivery of Th-l-inducing IL-1 8 gene was able to shorten by 2 weeks, the CTL induction time, and to incre ase the antigen-induced secretion of IL-2 and IFN-gamma. Furthermore, IL-18 co-delivery enhanced antigen-specific lymphoproliferative responses, and t his was most evident in mice that were primed and boosted with plasmid DNA. However, the induction of detectable antibodies in mice required two DNA v accinations and a protein boost. In contrast to the effects on cell-mediate d immunity, co-administration of IL-18-plasmid resulted in decreased antibo dy titers against viral proteins. (C) 2001 Elsevier Science Ltd. All rights reserved.