Factors associated with the development of neonatal tolerance after the administration of a plasmid DNA vaccine.
A plasmid DNA vaccine encoding the circumsporozoite protein of malaria (pCSP) induces tolerance rather than immunity when administered to newborn mice. We find that this tolerance persists for >1 yr after neonatal pCSP administration and interferes with the induction of protective immunity in animals challenged with live sporozoites. Susceptibility to tolerance induction wanes rapidly with age, disappearing within 1 wk of birth. Higher doses of plasmid are more tolerogenic, and susceptibility to tolerance is not MHC-restricted. CD8+ T cells from tolerant mice suppress the in vitro Ag-specific immune response of cells from adult mice immunized with pCSP. Similarly, CD8+ T cells from tolerant mice transfer nonresponsiveness to naive syngeneic recipients. These findings clarify the cellular basis and factors contributing to the development of DNA vaccine-induced neonatal tolerance.
Ichino
M
M
Section of Retroviral Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Mor
G
G
Conover
J
J
Weiss
W R
WR
Takeno
M
M
Ishii
K J
KJ
Klinman
D M
DM
D000818:Animals; D000831:Animals, Newborn / Q000235:genetics / Q000276:immunology*; D004198:Disease Susceptibility; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007108:Immune Tolerance / Q000235:genetics; D007111:Immunity, Cellular / Q000235:genetics; D007273:Injections, Intramuscular; D008288:Malaria / Q000235:genetics / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D010967:Plasmodium yoelii / Q000235:genetics / Q000276:immunology; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D015800:Protozoan Proteins; D019444:Vaccines, DNA; C041595:circumsporozoite protein, Protozoan