Induction of neonatal tolerance by plasmid DNA vaccination of mice

Plasmid DNA vaccines capable of preventing viral, bacterial, and parasitic infections are currently under development, Our labs have shown that 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, cytokine or cytotoxic responses when rechallenged a with DNA vaccine in vitro or in vivo. Tolerance was specific for immunogenic epitopes expressed by the vaccine-encoded, endogenously produced antigen. Mice challenged with exogenous circumsporozoite protein produced antibodies against 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.