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. Neonatally tolerized animals were unable to mount antibody, cytokine or cytotoxic responses when rechallenged 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.
Mor
G
G
Section of Retroviral Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Yamshchikov
G
G
Sedegah
M
M
Takeno
M
M
Wang
R
R
Houghten
R A
RA
Hoffman
S
S
Klinman
D M
DM
D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004247:DNA / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D007108:Immune Tolerance / Q000276:immunology*; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D010957:Plasmids / Q000276:immunology; D010967:Plasmodium yoelii / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology; D013154:Spleen / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
D000939:Epitopes; D017780:Malaria Vaccines; D010446:Peptide Fragments; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; D015847:Interleukin-4; D007371:Interferon-gamma; D004247:DNA