Intranasal CpG-oligodeoxynucleotide is a potent adjuvant of vaccine against Helicobacter pylori, and T helper 1 type response and interferon-gamma correlate with the protection.
BACKGROUND
Although a series of vaccines against Helicobacter pylori have emerged in the past 10 years, the mechanism involved in their protective effect is yet to be elucidated, and more effective vaccine adjuvants remain to be developed. In this study, CpG-oligodeoxynucleotide (CpG-ODN) was investigated as a new candidate for a H. pylori vaccine adjuvant. Furthermore, the role of T helper 1 (Th1) type response and interferon (IFN)-gamma in the protective immunity was explored.


METHODS
C57BL/6 mice and IFN-gamma knockout mice were intranasally or orally immunized with H. pylori whole cell sonicate (WCS)/CpG-ODN and challenged with different doses [5 x 10(8) and 5 x 10(6) colony-forming units (CFU)] of H. pylori. The protective effect was assessed as the percentage of noninfected mice. The responsive antibodies and cytokines were analyzed using an enzyme-linked immunosorbent assay (ELISA) and flow cytometry.


RESULTS
The prevention rates against H. pylori infection in mice intranasally immunized with WCS plus CpG-ODN were dramatically higher than those in sham-immunized mice (70% vs. 0%, challenged with 5 x 10(8) CFU H. pylori; 90% vs. 20%, challenged with 5 x 10(6) CFU H. pylori). Significantly higher levels of immunoglobulin G2a (IgG2a) and IFN-gamma were detected in the mice immunized with WCS/CpG than in sham-immunized controls. However, vaccination failed to effectively protect IFN-gamma knockout mice challenged with H. pylori.


CONCLUSIONS
CpG-ODN given intranasally is a potent adjuvant for development of a H. pylori vaccine. Th1-type response and IFN-gamma are involved in the protection.
Shi
Tong
T
Ren Ji Hospital, Shanghai Institute of Digestive Disease, Shanghai Second Medical University, Shanghai, China 20001.
Liu
Wen-zhong
WZ
Gao
Fei
F
Shi
Gui-ying
GY
Xiao
Shu-dong
SD
D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000276:immunology*; D015169:Colony Count, Microbial; D005753:Gastric Mucosa / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000276:immunology*; D007371:Interferon-gamma / Q000032:analysis* / Q000235:genetics; D015847:Interleukin-4 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014510:Urease / Q000032:analysis; D014611:Vaccination / Q000379:methods
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D015847:Interleukin-4; D007371:Interferon-gamma; D014510:Urease