Oligonucleotide containing CpG motifs enhances immune response to mucosally or systemically administered tetanus toxoid

Abstract

Oligodeoxynucleotides (ODN) containing unmethylated CpG dinucleotides induce proliferation of B cells and activation of macrophages and thus stimulation of the immune system. We tested an oligonucleotide containing an unmethylated CpG dinucleotide flanked by two 5′ purines and two 3′ pyrimidines (GAGAA CG CTCGACCTTCGAT) for the ability to affect antibody levels to tetanus toxoid (Tt). Groups of male Rowett rats ( n=5–6/group) received colloidal aluminium hydroxide (Al(OH) 3) either alone, or with Tt bound to the Al(OH) 3, or with Tt bound to Al(OH) 3 with the addition of the CpG oligonucleotide. Antigens were administered subcutaneously in the salivary gland vicinity once, or by gastric intubation on 3 consecutive days. On day 124 all animals were given a boost with the same material by the same route. Serum IgG and saliva IgA antibody to Tt was determined by ELISA. Serum antibody levels were significantly higher in ODN+Tt treated rats than in Tt-alone rats immunized by either route after primary or booster immunizations. Thus, administration of an ODN containing unmethylated CpG motifs along with an immunogen bound to Al(OH) 3 can result in enhanced specific antibody when administered by intragastric as well as subcutaneous routes.