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Mucosal Immunization with Helicobacter, CpG DNA, and Cholera Toxin Is Protective

Weiwen Jiang, Henry J. Baker, and Bruce F. Smith^*

Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, Alabama 36849

Received 29 May 2002/ Returned for modification 17 July 2002/ Accepted 19 September 2002

The mucosal delivery of antigens requires an effective adjuvant to induce mucosal immunity. Current mucosal adjuvants include cholera toxin (CT) and Escherichia coli heat-labile toxin. Unmethylated CpG immunostimulatory oligodeoxynucleotides (ODNs) have been proposed as novel mucosal adjuvants. In this study, mice were immunized with sonicated Helicobacter felis with CT and/or CpG ODN adjuvants. All groups receiving either adjuvant singly or in combination developed increased serum anti-H. felis immunoglobulin G (IgG). The addition of either CpG or CT, or both, produced a specific fecal anti-H. felis IgA response, with the highest IgA levels occurring in animals immunized intranasally with sonicated H. felis with CT and CpG. Following H. felis challenge, addition of the adjuvant CpG ODN provided no significant protection, while groups given CT showed a high degree of protection, although not complete. When CpG ODN was combined with CT and the vaccine combination was delivered intranasally, no bacterial colonization was detected by quantitative PCR, providing "sterile immunity" and demonstrating synergy between CpG ODN and CT.

Editor: J. D. Clements

Present address: Division of Infectious Diseases, Department of Medicine, Duke University, Durham, NC 27705.

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