INDUCTION OF NEONATAL TOLERANCE BY PLASMID DNA VACCINATION OF MICE

Plasmid DNA vaccines capable of preventing viral, bacterial, and paras itic infections are currently under development, Our labs have shown t hat a plasmid DNA vaccine encoding the circumsporozoite protein of the malaria parasite elicits protective immunity against live sporozoite challenge in adult BALB/c mice. We now find that the same DNA vaccine induces tolerance rather than immunity when administered to 2-5 d-old mice, Neonatal, tolerized animals were unable to mount antibody, cytok ine or cytotoxic responses when rechallenged a with DNA vaccine in vit ro or in vivo. Tolerance was specific for immunogenic epitopes express ed by the vaccine-encoded, endogenously produced antigen. Mice challen ged with exogenous circumsporozoite protein produced antibodies agains t a different set of epitopes, and were not tolerized, These findings demonstrate important differences in the nature and specificity of the immune response elicited by DNA vaccines versus conventional protein immunogens.