Mucosal delivery of CpG
oligodeoxynucleotide (ODN) in mice has been shown to induce potent innate immunostimulatory responses and protection against
infection. We evaluated the efficacy of
CpG ODN in stimulating systemic innate immune responses in sheep following delivery to the pulmonary mucosa. Intrapulmonary (IPM) administration of B-Class
CpG ODN in saline induced transient systemic responses which included increased rectal temperatures, elevated serum 2'5'-A
synthetase and
haptoglobin concentrations. The ODN dose required to induce detectable systemic responses following IPM delivery could be reduced by approximately 80% if the
CpG ODN was administered in 30% emulsigen instead of saline. Intrapulmonary B-Class
CpG ODN formulated in 30% emulsigen produced similar effects when compared to those seen following SC injection. These responses were
CpG ODN-specific since control GpC ODN did not induce any detectable response. Intrapulmonary administration of both B-Class and the newly described C-Class
CpG ODN produced similar effects indicating that both classes of
CpG ODN were comparably effective in stimulating innate immune system following mucosal delivery. Administration of
CpG ODN directly into the lungs or delivery of
CpG ODN via an intratracheal (IT) infusion also produced similar systemic responses. These observations support the conclusion that mucosal delivery of
CpG ODN is an effective route for induction of systemic
acute phase responses and
antiviral effector molecules in large animals, and may be helpful in controlling systemic
infections.