Helicobacter pylori as a Vaccine Delivery System

Abstract

For more than 10 years a vaccine against Helicobacter pylori has been the elusive goal of many investigators. The need for a vaccine was highlighted when eradication attempts in developing countries were foiled by reinfection rates of 15-30% per annum. In addition, physicians in developed countries were concerned that attempts at total eradication of H. pylori would result in widespread macrolide resistance in both H. pylori and other important pathogens. Although attempts to produce vaccines against H. pylori have failed in their ultimate goal, considerable knowledge has been developed on the pathogenesis and immunology of Helicobacter infections. In this article we describe an alternative use for this new knowledge, i.e. a plan to use live Helicobacter species to deliver vaccines against other organisms. Because of its intimate attachment to the gastric mucosa and long-term residence there, H. pylori might succeed as an antigen delivery system, a goal which has eluded most other strategies of nonparenteral vaccination.

Expansion of the Tetracycline-Dependent Regulation Toolbox for Helicobacter pylori

“…This system achieved large regulatory windows (up to 80-fold induction) and also was shown to be regulated in the mouse model of infection. This system is highly suitable for applications such as differential gene regulation during infection studies, heterologous antigen expression using H. pylori as a vaccine platform (37,43), or investigating the function of the numerous antisense RNAs in H. pylori (44,45) by inducing their overexpression. As such, the utility of this system has been expanded through the development of the H. pylori tet promoters described here.…”

Case Histories of Significant Medical Advances: Eradicating Helicobacter Pylori Infections to Treat Ulcers

“…On the basis of these results, European regulators approved Astra's PPI in 1988, and American regulators followed in 1990. f By 1993, Swedish and Australian researchers had shown that a PPI combined with antibiotics healed ulcers and eradicated H. pylori infections faster than other combinations, with the lowest rates of ulcer recurrence. 34 Research on drug combinations in the U.S. benefitted from the FDA's loose enforcement of rules for testing new uses for already approved drugs. Although in principle the FDA requires pre-approval of such tests, in practice it often does not penalize researchers who do not seek pre-approval.…”

Antigen Delivery System II

“…More protective antigen was delivered to the cell surface and secreted by the hemolysis system and, after oral administration, this construct also induced some protection to challenge with a virulent RDEC strain. Marshall and Schoep (2007) review efforts, so far unsuccessful, to develop an attenuated H. pylori antigen delivery strategy to induce protective immunity to other pathogens.…”