The immune response to a DNA vaccine can be modulated by co-delivery of cytokine genes using a DNA prime-protein boost strategy

A large-scale DNA vaccination trial was performed in sheep to investigate w hether co-delivery of the cytokine genes IL-4, IL-5, IL-15, GM-CSF or IFN-g amma could modulate the immune response generated to an antigen, in a DNA p rime-recombinant protein boost regime. Vaccination with the recombinant EG9 5 protein has been shown to induce protection in sheep from Echinococcus gr anulosus infection, the causative agent of hydatid disease. Here we demonst rate that vaccination with DNA encoding EG95 effectively primed the humoral response, as judged by high IgG anti-EG95 titres detected one-week after a boost with the recombinant protein. However, by two weeks after protein-bo ost the titres in the control group had reached levels similar to the group s primed with EG95 DNA. Priming with two doses of DNA vaccine followed by b oosting with recombinant protein induced a predominantly IgG1 response. In contrast, priming and boosting with the protein vaccine generated a strong IgG2 response. Go-delivery of the EG95 DNA vaccine with DNA encoding GM-CSF enhanced the antibody titre to EG95 while co-delivery of IFN-gamma or IL-4 encoding DNA appeared to reduce the ability of the DNA vaccine to prime an IgG antibody response. This study has demonstrated the efficacy of the co- delivery of cytokines to modulate immune responses generated in a DNA prime -protein boost strategy. (C) 2001 Elsevier Science Ltd. All rights reserved .