CpG oligodeoxynucleotides as vaccine adjuvants in primates.
Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs act as immune adjuvants in mice, boosting the humoral and cellular response to coadministered Ags. CpG ODN that stimulate human PBMC are only weakly active in mice. Thus, alternative animal models are needed to monitor the activity and safety of "human" CpG ODN in vivo. This work demonstrates that rhesus macaques recognize and respond to the same CpG motifs that trigger human immune cells. Coadministering CpG ODN with heat-killed Leishmania vaccine provided significantly increased protection of macaques against cutaneous Leishmania infection. These findings indicate that rhesus macaques provide a useful model for studying the in vivo activity of human CpG motifs, and that ODN expressing these motifs act as strong immune adjuvants.
Verthelyi
Daniela
D
Divisions of. Viral Products and Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research/Food and Drug Administration, Bethesda, MD 20892, USA.
Kenney
Richard T
RT
Seder
Robert A
RA
Gam
Albert A
AA
Friedag
Brenda
B
Klinman
Dennis M
DM
D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007700:Kinetics; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D009838:Oligodeoxyribonucleotides / Q000009:adverse effects / Q000494:pharmacology*; D016052:Protozoan Vaccines; D015164:Vaccines, Inactivated
D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; C408982:CPG-oligonucleotide; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D016052:Protozoan Vaccines; D015164:Vaccines, Inactivated