Effects of Oral Vaccination and Immunomodulation by Cholera Toxin on ExperimentalHelicobacter pyloriInfection, Reinfection, and Gastritis

Abstract

Therapeutic vaccination is an attractive strategy to control infection and disease caused by Helicobacter pylori. In mice infected with H. pylori we have studied the protective effect of oral immunization with an H. pylori lysate preparation given together with the mucosal adjuvant cholera toxin (CT), both against the initial infection and against a later reinfection challenge. We have also examined the effects of treatment with the CT adjuvant alone on H. pylori infection and reinfection. Specific immunization with lysate was found to result in a sixfold reduction of the extent (bacterial load) of the primary infection and also to provide similar levels of protection against reinfection. However, these effects were associated with severe postimmunization gastritis. In contrast, oral treatment with CT alone at the time of initial infection, while unable to suppress the initial infection, gave rise to a 20-fold reduction in bacterial load upon reinfection without causing any associated gastric inflammation. Both the infected animals that were specifically immunized and those that were treated with CT only displayed increased in vitro proliferative responses of mononuclear cells to H. pylori antigens. Antibody levels in response to H. pylori were on the other hand only marginally increased after treatment with CT, whereas they were markedly elevated after immunization with lysate plus CT, with a rise in both (Th2-driven) immunoglobulin G1 (IgG1) and, especially, (Th1-driven) IgG2a antibodies. The results illustrate the complex balance between protection and harmful inflammation after postinfection vaccination against H. pylori as studied in a mouse model.

A Double Mutant Heat-Labile Toxin from Escherichia coli, LT(R192G/L211A), Is an Effective Mucosal Adjuvant for Vaccination against Helicobacter pylori Infection

“…The bacteria were cultured in liquid broth as previously described (14). Before infection of mice, the optical density (OD) of the bacteria was adjusted to 1.5, and 300 l, corresponding to approximately 3 ϫ 10 8 viable bacteria, was administered intragastrically to each mouse (15).…”

Vacunas en desarrollo: Helicobacter pylori

“…En ratones BALB/c, Kim y cols 21 reportaron reducción significativa de la carga bacteriana asociada a la inmunización con lisados de SS1 más TC, reducción no observable en ratones C57BL/6. Por otro lado, Ravhagan y cols 22 observaron con protocolos de inmunización terapéuti-ca similares, una reducción significativa de la carga bacteriana al utilizar ratones con el mismo background (C57BL/6) 22 , sugiriendo que es indispensable que la cepa vacuna tenga el mismo antígeno de Lewis en su LPS que la cepa empleada en el desafío, para lograr algún efecto protector 23 . La utilización de cepas atenuadas de Salmonella que expresan antígenos a elección es una alternativa a los protocolos de vacunación con lisados totales.…”

Sublingual Immunization Protects against Helicobacter pylori Infection and Induces T and B Cell Responses in the Stomach

“…A reduction in bacterial counts in immunized compared to unimmunized mice was used as a measure of protection (23). Protection factors were calculated as the ratio of the geometric mean number of bacteria in infected control mice to the number of bacteria in individual vaccinated mice (28). We have previously shown comparable protection against H. pylori SS1 infection when immunizing IG with CT-adjuvanted H. pylori lysate antigens from strain Hel 305 or SS1 (27).…”

“…The bacteria were grown for 3 days on Columbia iso-agar plates and further cultured overnight in brucella broth (Becton Dickinson Biosciences [BD], San Diego, CA) under microaerophilic conditions. Before infection of mice, the optical density (OD) of the bacteria was adjusted to 1.5, corresponding to approximately 1 ϫ 10 9 viable bacteria/ml (28).…”