Department of Microbiology, Faculty of Medicine, Kuwait University, Jabriya, Kuwait.
mBio. 2013 May 7;4(3):e00246-13. doi: 10.1128/mBio.00246-13.
Immunity to Campylobacter jejuni, a major diarrheal pathogen, is largely Penner serotype specific. For broad protection, a vaccine should be based on a common antigen(s) present in all strains. In our previous study (M. J. Albert, S. Haridas, D. Steer, G. S. Dhaunsi, A. I. Smith, and B. Adler, Infect. Immun. 75:3070-3073, 2007), we demonstrated that antibody to cholera toxin (CT) cross-reacted with the major outer membrane proteins (MOMPs) of all Campylobacter jejuni strains tested. In the current study, we investigated whether immunization with CT protects against intestinal colonization by C. jejuni in an adult mouse model and whether the nontoxic subunit of CT (CT-B) is the portion mediating cross-reaction. Mice were orally immunized with CT and later challenged with C. jejuni strains (48, 75, and 111) of different serotypes. Control animals were immunized with phosphate-buffered saline. Fecal shedding of challenge organisms was studied daily for 9 days. Serum and fecal antibody responses were studied by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. The cross-reactivity of rabbit CT-B antibody to MOMP was studied by immunoblotting. The reactivity of 21 overlapping 30-mer oligopeptides (based on MOMP's sequence) against rabbit CT antibody was tested by ELISA. Test animals produced antibodies to CT and MMP in serum and feces and showed resistance to colonization, the vaccine efficacies being 49% (for strain 48), 37% (for strain 75), and 34% (for strain 111) (P, ≤0.05 to ≤0.001). One peptide corresponding to a variable region of MOMP showed significant reactivity. CT-B antibody cross-reacted with MOMP. Since CT-B is a component of oral cholera vaccines, it might be possible to control C. jejuni diarrhea with these vaccines.
Campylobacter jejuni is a major cause of diarrhea worldwide. Patients who recover from C. jejuni diarrhea develop immunity to the infecting serotype and remain susceptible to infection with other serotypes. A vaccine based on a common protective antigen(s) present in all C. jejuni serotypes is expected to provide broad protection. In our previous study, we showed that antibody to cholera toxin (CT) reacted with the major outer membrane proteins (MOMPs) from different strains of C. jejuni. We assumed that the B subunit of the toxin (CT-B), which is nontoxic and a component of licensed oral cholera vaccines, might be the component that cross-reacts with MOMP. In the current study, we showed that orally immunizing mice with CT protected them against colonization upon challenge with different serotypes of C. jejuni. We also showed that CT-B is the component mediating cross-reaction. Therefore, it might be possible to use cholera vaccines to prevent C. jejuni diarrhea. This could result in significant savings in vaccine development and treatment of the disease.
空肠弯曲菌是世界范围内腹泻的主要病原体之一。感染空肠弯曲菌后痊愈的患者对感染血清型产生免疫力，但仍易感染其他血清型。基于所有空肠弯曲菌血清型中存在的共同保护性抗原的疫苗有望提供广泛的保护。在我们之前的研究中，我们表明霍乱毒素（CT）抗体与不同空肠弯曲菌菌株的主要外膜蛋白（MOMP）反应。我们假设毒素的 B 亚单位（CT-B），它是无毒的，也是许可的口服霍乱疫苗的组成部分，可能是与 MOMP 发生交叉反应的成分。在目前的研究中，我们表明用 CT 对小鼠进行口服免疫可防止它们在受到不同血清型空肠弯曲菌的挑战时发生定植。我们还表明 CT-B 是介导交叉反应的成分。因此，使用霍乱疫苗预防空肠弯曲菌腹泻是可能的。这可能会节省大量的疫苗开发和疾病治疗成本。
