Subcutaneous, but not intratracheal administration of the TLR9 agonist, CpG DNA transiently reduces parainfluenza-3 virus shedding in newborn lambs

Abstract Synthetic oligodeoxynucleotides (ODN) containing CpG motifs signal through TLR9 and activate innate immunity resulting in protection against a variety of parasitic, bacterial and viral pathogens in mouse models. However, few studies have demonstrated protection in humans and large animals....

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Bibliographic Details
Published in:Comparative immunology, microbiology and infectious diseases microbiology and infectious diseases, 2010-12, Vol.33 (6), p.e111-e117
Main Authors: Nichani, Anil K, Dar, M. Arshad, Mirakhur, Kuldip K, Krieg, Arthur M, Booth, Jayaum S, Townsend, Hugh G.G, Potter, Andrew A, Babiuk, Lorne A, Mutwiri, George K
Format: Article
Language:English
Subjects:
2',5'-Oligoadenylate Synthetase - blood
Allergy and Immunology
Animals
Animals, Newborn
CpG Islands
CpG ODN
Female
Immunity, Innate
Infectious Disease
Injections, Subcutaneous
Innate immunity
Male
Neonates
Oligodeoxyribonucleotides - administration & dosage
Parainfluenza Virus 3, Bovine - physiology
Parainfluenza-3 virus
Respirovirus Infections - immunology
Respirovirus Infections - virology
Sheep
Toll-Like Receptor 9 - agonists
Toll-like receptors
Trachea
Virus Shedding - drug effects
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Summary:Abstract Synthetic oligodeoxynucleotides (ODN) containing CpG motifs signal through TLR9 and activate innate immunity resulting in protection against a variety of parasitic, bacterial and viral pathogens in mouse models. However, few studies have demonstrated protection in humans and large animals. In the present investigations, we evaluated protection by CpG ODN in a parainfluenza-3 (PI-3) virus infection in neonatal lambs. Subcutaneous (SC) injection of CpG ODN induced high levels of 2′5′-A synthetase and significantly reduced PI-3 virus shedding in newborn lambs. Furthermore, pre-treatment of newborn lambs with SC CpG ODN 2 days, but not 6 days prior to the virus challenge was protective. In contrast, intratracheal (IT) administration of CpG ODN induced 2′5′-A synthetase but had no significant impact on PI-3 virus shedding in nasal secretions. We conclude that a systemic administration of CpG ODN and the timing of the treatment are critical for the protection of neonatal lambs against a respiratory viral infection.
ISSN:0147-9571
1878-1667
DOI:10.1016/j.cimid.2010.06.003