Immunoadjuvant action of plasmid DNA in liposomes

Bacterial DNA and oligodeoxynucleotides containing immunostimulatory sequen ces with a CpG motif stimulated a Th1 type response in vivo. The adjuvant a ction of a non-coding plasmid DNA derived from pRc/CMV HBS (encoding the S region of hepatitis B surface antigen, HBsAg) in mice was investigated. The role of methylation on the adjuvanticity of the plasmid as well as the eff ect of vaccine formulation employed on the outcome of antigen-specific humo ral and cellular responses were also studied. The results demonstrated that plasmid DNA acted as a Th1 promoting adjuvant when mixed as such or co-ent rapped in liposomes with a very low dose of antigen. However. the adjuvant activity was lost when separate liposome entrapped formulations of both the antigen and the plasmid DNA were mixed, indicating a necessity for the ant igen and the plasmid DNA to contact the same APC for optimal immune activat ion. A decreased adjuvanticity of plasmid DNA upon methylation with HpaII m ethyltransferase was also demonstrated. A mechanism that may help partially explain the reduction in adjuvanticity after modification of C residues is also discussed. (C) 1999 Elsevier Science Ltd. All rights reserved.