Formulations of single or multiple H. pylori antigens with DC Chol adjuvant induce protection by the systemic route in mice Optimal prophylactic combinations are different from therapeutic ones

Abstract

The ability to induce a protective response against Helicobacter pylori infection has been investigated by systemic immunization of mice with urease formulated with the cationic lipid DC Chol. This compound acts both as a formulating agent and as an adjuvant and induces a balanced Th1/Th2 response shown to be more effective for protection in our previous studies. Urease-DC Chol induced a significant protection in prophylaxis but not in therapeutic immunization. The protection level was between 1.5 and 2 log reduction of bacterial density measured by quantitative culture compared to unimmunized-infected mice. In parallel, the protective efficacy of other H. pylori antigens formulated in a similar way and administered with DC Chol was tested. These antigens were tested alone or in combination in prophylactic and therapeutic regimens. Some combinations of antigens induced a better prophylactic or therapeutic activity than urease alone (0.5-1.5 log further reduction in prophylaxis and therapy respectively, P<0.05). The combinations that induced the best protection were different in prophylaxis and therapy. In conclusion, DC Chol provides a convenient and efficient method to formulate different antigens even when they are present in non-compatible buffers initially. Moreover, the results obtained in protection against H. pylori with such formulations should lead the way to future clinical trials.

Comparative proteomics and immunoproteomics of Helicobacter pylori related to different gastric pathologies☆

“…In the various preclinical animal models, vaccination has been shown to protect against H. pylori challenge infection [10]. Most of vaccines tested so far contain only one or two antigens, although recent studies suggested that combining several protective antigens could substantially increase vaccine efficacy [6,11,12]. Characterization of protein differences between strains may be of particular significance, indicating proteins which could be important as strain markers associated with specific clinical outcomes of H. pylori infection.…”

Unraveling the Complexity of <em>Helicobacter pylori</em> Pathogenicity: Insights into Outer Membrane Proteins, Virulence Factors, and Treatment Strategies

“…Hop B and Hop C are considered potential targets for vaccine therapy as they are involved during the early colonization stages of infection with H. pylori. In immunization studies in mice, when HopB, either on its own or in combination with other antigens (BabB, urease, catalase), was conjugated to the DC-Chol mucosal adjuvant, enhanced cellular and humoral protective responses were observed [208]. In a further promising evaluation of HopB immunogenicity in recombinant plasmids, HopB recombinant protein was introduced as a novel means of infection prophylaxis and eradication [209].…”

Helicobacter pylori Outer Membrane Proteins and Virulence Factors: Potential Targets for Novel Therapies and Vaccines

“…Hop B and Hop C are considered potential targets for vaccine therapy as they are involved during the early colonization stages of infection with H. pylori. In immunization studies in mice, when HopB, either on its own or in combination with other antigens (BabB, urease, catalase), was conjugated to the DC-Chol mucosal adjuvant, enhanced cellular and humoral protective responses were observed [185]. In a further promising evaluation of HopB immunogenicity in recombinant plasmids, HopB recombinant protein was introduced as a novel means of infection prophylaxis and eradication [186].…”