Prevention of neonatal tolerance by a plasmid encoding granulocyte-macrophage colony stimulating factor.
A plasmid DNA vaccine encoding the circumsporozoite protein of malaria (pCSP) 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 eliciting a primary IgG anti-CSP immune response. Mice primed as neonates and boosted as adults mounted anamnestic responses characterized by high serum antibody titers, cytotoxic T-cell activity and antigen-specific interferon gamma (IFNgamma) production. Neonatal administration of pGMCSF accelerated the maturation of local dendritic cells, suggesting that APC function plays a key role in determining whether tolerance or immunity results from neonatal exposure to antigen.
Ishii
K J
KJ
Retroviral Immunology Section, Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Weiss
W R
WR
Klinman
D M
DM
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000008:administration & dosage / Q000276:immunology; D010967:Plasmodium yoelii / Q000235:genetics / Q000276:immunology; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D000953:Antigens, Protozoan; D015800:Protozoan Proteins; D019444:Vaccines, DNA; C041595:circumsporozoite protein, Protozoan; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor