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Infection and Immunity, August 2005, p. 4948-4954, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4948-4954.2005

Prevention and Treatment of Cutaneous Leishmaniasis in Primates by Using Synthetic Type D/A Oligodeoxynucleotides Expressing CpG Motifs

Barbara Flynn,^2, Vivian Wang,^1, David L. Sacks,³ Robert A Seder,² and Daniela Verthelyi^1*

Division of Therapeutic Proteins, Center for Drug Evaluation and Review, Food and Drug Administration, Washington, D.C.,¹ Vaccine Research Center,² Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland³

Received 23 September 2004/ Returned for modification 11 November 2004/ Accepted 21 March 2005

Oligodeoxynucleotides (ODN) containing CpG motifs mimic microbial DNA and are recognized by toll-like receptor 9 on immune cells. The resulting response limits the early spread of infectious organisms and promotes the development of adaptive immunity. In this regard, CpG ODN show promise as immunoprotective agents and as vaccine adjuvants. Previous studies of nonhuman primates showed that administration of CpG ODN type D (also known as type A) at the site of infection 3 days before and after a challenge with Leishmania major enhanced host resistance and reduced the lesion's severity. In this study, we show that systemic administration of D/A ODN limits the size of lesions following an intradermal infection with L. major. Importantly, the reduced morbidity was not associated with a reduction in long-term immunity, as such treated macaques were still protected following a secondary challenge. Finally, administration of D/A ODN to macaques that had established cutaneous lesions reduced the severity of the lesions, suggesting a potential role for CpG ODN in L. major treatment. Together, these findings support the development of clinical studies to assess the use of CpG ODN types D/A as immunoprotective and therapeutic agents.

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* Corresponding author. Mailing address: Bldg 29A Rm 3B19, 8800 Rockville Pike, Bethesda, MD 20892. Phone: (301) 827-1702. Fax: (301) 480-3256. E-mail: Verthelyi{at}cber.fda.gov.

Editor: J. F. Urban, Jr.

Barbara Flynn and Vivian Wang contributed equally to this work.

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Infection and Immunity, August 2005, p. 4948-4954, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4948-4954.2005

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