The effect of CpG sequences on the B cell response to a viral glycoproteinencoded by a plasmid vector

The effect of palindromic CpG sequences on the B cell response to plasmid v ectors expressing a highly immunogenic viral glycoprotein was investigated. Methylation of the CpG sequences of bacterial expression vectors abolished their ability to induce an antibody response to the transgene product in m ice. The antibody response could be rescued by concomitant injection of oli gonucleotides carrying immunostimulatory sequences. The B cell response to two plasmid vectors, both expressing the same viral glycoprotein but contai ning a different content of the highly stimulatory AACGTT motif, was compar ed. Comparable B cell responses were induced to the two constructs given at an optimal vaccine dose while the Vector containing additional palindromic sequences resulted in higher antibody titers at a suboptimal dose. These d ata indicate that deletion of CPG motifs or methylation of such sequences i n plasmid DNA can abrogate the immune response to the vector encoded antige n and might thus enhance their usefulness as gene therapy vehicles.