Effect of calcium carbonate encapsulation on the activity of orally administered CpG oligonucleotides

Authors

• N Kayraklioglu
• J Scheiermann
• WG Alvord
• DM Klinman

Abstract

Synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) stimulate immune cells via TLR9. As ODN are susceptible to gastric degradation, clinical trials designed to evaluate their therapeutic utility have relied solely on parenteral routes of administration. A strategy to improve the activity of orally delivered ODN by reducing their susceptibility to GI digestion via encapsulation in calcium carbonate nanoparticles (ODNcap) was recently described. This study compares the in vitro and in vivo activity of encapsulated (ODNcap) vs free CpG ODN delivered orally or parenterally. ODNcap mirrored the ability of free ODN to stimulate splenic B cells and macrophages in vitro. ODNcap activated immune cells in the Peyer’s patches and mesenteric lymph nodes after oral delivery. Their effect on GI immunity was evaluated in studies of DSS-induced colitis and enteric infection while systemic immunity was examined by monitoring their effect on LPS-induced cytokine production and systemic pathogen challenge. Results indicate that orally delivered CpG ODN predominantly induce gastrointestinal rather than systemic immunity and that calcium carbonate encapsulation does not significantly alter this behavior.

Scientific Focus Area: Immunology

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