Prevention of neonatal tolerance by a plasmid encoding granulocyte-macrophage colony stimulating factor

A plasmid DNA vaccine encoding the circumsporozoite protein of malaria (pCS P) induces protective immunity in adult mice but persistent tolerance when administered to neonates. In an effort to improve antigen presenting cell ( APC) function in newborns, we co-administered pCSP with a plasmid encoding granulocyte-macrophage colony stimulating factor (pGMCSF). This combination of plasmids prevented the development of neonatal tolerance, instead elici ting a primary IgG anti-CSP immune response. Mice primed as neonates and bo osted as adults mounted anamnestic responses characterized by high serum an tibody titers, cytotoxic T-cell activity and antigen-specific interferon ga mma (IFN gamma) production. Neonatal administration of pGMCSF accelerated t he maturation of local dendritic cells, suggesting that APC function plays a key role in determining whether tolerance or immunity results from neonat al exposure to antigen. Published by Elsevier Science Ltd.