title: The effect of CpG sequences on the B cell response to a viral glycoprotein encoded by a plasmid vector.
abstract: The effect of palindromic CpG sequences on the B cell response to plasmid vectors 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 mice. The antibody response could be rescued by concomitant injection of oligonucleotides carrying immunostimulatory sequences. The B cell response to two plasmid vectors, both expressing the same viral glycoprotein but containing a different content of the highly stimulatory AACGTT motif, was compared. 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 data indicate that deletion of CpG motifs or methylation of such sequences in plasmid DNA can abrogate the immune response to the vector encoded antigen and might thus enhance their usefulness as gene therapy vehicles.
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: S
authors.initials: S
authors.lastname: Pasquini
authors.forename: H
authors.initials: H
authors.lastname: Deng
authors.forename: S T
authors.initials: ST
authors.lastname: Reddy
authors.forename: W
authors.initials: W
authors.lastname: Giles-Davis
authors.forename: H C
authors.initials: HC
authors.lastname: Ertl
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D018899:CpG Islands / Q000276:immunology*; D003587:Cytomegalovirus / Q000235:genetics* / Q000276:immunology; D015257:DNA-Cytosine Methylases / Q000494:pharmacology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011820:Rabies virus / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D014759:Viral Envelope Proteins; C081573:DNA modification methylase SssI; D015257:DNA-Cytosine Methylases