Immunostimulatory DNA pre-priming: a novel approach for prolonged Th1-biased immunity.
Immunostimulatory DNA sequences (ISS) have been shown to promote CTL and Th1 immune responses to coinjected antigens. This phenomenon can be attributed to the capacity of ISS to induce the secretion of type-1 cytokines and to up regulate costimulatory ligands on antigen-presenting cells. We hypothesized that ISS administration prior to antigen administration (prepriming), via the mechanisms stated above, would Th1 bias immune responses to subsequently injected antigens for an extended period of time. The data presented show that ISS provide in vivo adjuvant activity for up to 2 weeks after intradermal or intranasal delivery. Furthermore, the results demonstrate that ISS prepriming can induce immune responses that are significantly stronger than with ISS/antigen covaccination. ISS prepriming offers an alternative approach to the traditional use of adjuvants (i.e., antigen/adjuvant coinjection) and expands the potential clinical applications for ISS.
Kobayashi
H
H
Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093-0663, USA.
Horner
A A
AA
Takabayashi
K
K
Nguyen
M D
MD
Huang
E
E
Cinman
N
N
Raz
E
E
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics*; D000281:Administration, Intranasal; D000818:Animals; D018899:CpG Islands / Q000276:immunology; D004269:DNA, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D007070:Immunoglobulin A / Q000096:biosynthesis; D007271:Injections, Intradermal; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D013873:Thionucleotides / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013997:Time Factors
D000276:Adjuvants, Immunologic; D004269:DNA, Bacterial; D007070:Immunoglobulin A; D009838:Oligodeoxyribonucleotides; D013873:Thionucleotides