A CpG oligonucleotide can protect mice from a low aerosol challenge dose of Burkholderia mallei

Abstract

Treatment with an oligodeoxynucleotide (ODN) containing CPG motifs (CpG ODN 7909) was found to protect BALB/c mice from lung infection or death after aerosol challenge with Burkholderia mallei. Protection was associated with enhanced levels of gamma interferon (IFN-gamma)-inducible protein 10, interleukin-12 (IL-12), IFN-gamma, and IL-6. Preexposure therapy with CpG ODNs may protect victims of a biological attack from glanders.

FIG. 1.

CPG 7909 pretreatment can reduce the numbers of microorganisms in the spleens of infected mice. Mice were injected i.p. with HBSS, CPG 7909, or CpG 2216 48 h before aerosol challenge with B. mallei. Five days after challenge, the numbers (geometric mean) of bacteria in the spleens of infected mice were determined. Bars indicate ±1 standard error.

FIG. 2.

CPG 7909 pretreatment can eliminate or reduce the numbers of microorganisms in the lungs of infected mice. Mice were injected i.p. with HBSS (▪), CPG 7909 (░⃞), or CpG 2216 (▨) 48 h before aerosol challenge with B. mallei. Five, 11, and 18 days after challenge, the numbers (geometric mean) of bacteria in the lungs of infected animals were determined. Bars indicate ±1 standard error.

FIG. 3.

(A) CPG 7909 given 48 h before or on the day of challenge can protect mice from lethality due to B. mallei challenge. Mice were injected i.p. with HBSS (♦) or CPG 7909 48 h before challenge (▪), the day of challenge (▴), or 24 h (•) after aerosol challenge with B. mallei. (B) CpG 2216 pretreatment does not protect mice from lethality due to B. mallei challenge. Mice were injected i.p. with HBSS (♦) or CpG 2216 (▪) 48 h before challenge with B. mallei.

FIG. 4.

CpG ODN pretreatment can increase the levels of IP-10 in plasma (A) and BAL fluid (B), IL-12 in plasma (C) and BAL fluid (D), IL-6 in plasma (E) and BAL fluid (F), and IFN-γ in plasma (G). Mice were injected i.p. with CPG 7909 (♦), CpG 2216 (▪), or ODN 2137 (▴) 3, 6, 24, or 48 h before determination of chemokine/cytokine concentration. *, statistical significance of at least P < 0.05 between chemokine/cytokine levels stimulated by CpG ODN and levels stimulated by control ODN 2137. Actual levels of statistical significance are found in the text.