Oral Immunization with Recombinant Helicobacter pylori Urease Induces Secretory IgA Antibodies and Protects Mice from Challenge with Helicobacter felis

Abstract

Helicobacter pylori, a gram-negative spiral bacterium, is the cause of chronic superficial (type B) gastritis and peptic ulcer disease. The urease enzyme of H. pylori was expressed as an inactive recombinant protein in Escherichia coli, purified as particulate structures of 550-600 kDa molecular mass with a diameter of approximately 12 nm. Given orally, 5 micrograms of urease with an appropriate mucosal adjuvant, such as the labile toxin of E. coli, protected 60%-100% of mice against challenge with virulent Helicobacter felis. Protection correlated with the level of secretory IgA antibodies against urease. Oral administration of antigen was as effective or better than intragastric administration. Parenteral injection of antigen or intragastric administration of high-dose antigen without adjuvant elicited serum IgG but no IgA antibodies and did not confer protection. Recombinant urease as an oral vaccine candidate deserves further investigation as an approach to the prevention of Helicobacter-induced chronic gastroduodenal diseases in humans.

Implications of Helicobacter pylori infection for stomach cancer prevention

“…Previous reports document successful protection against infection by Helicobacter felis in mice, using the following orally administered combinations: H. felis antigen plus adjuvant cholera toxin as well as the nontoxic cholera toxin B subunit (Lee, A. & Chen, 1994); recombinant H. pylori GroES-like heat shock proteins in combination with the B subunit of H. pylori urease (Ferrero et al, 1995); and recombinant H. pylori urease with adjuvant E. coli toxin (Lee, C. K. et al, 1995). Currently it is not known whether a similar protection against H. pylori infection of adequate duration can be achieved in humans.…”

Mucosal IgA & IL-1β in Helicobacter pylori Infection

“…Both these results lead to the conclusion that mucosal IgA level might be protecting the mucosa by lowering the bacterial density. Studies have suggested that locally produced antibodies, particularly IgA [13,14], might block H. pylori infection by preventing colonization and adhesion and allowing killing by neutrophils or monocytes through bacterial opsonisation [15,16]. Helicobacter-specific IgA monoclonal antibodies administered directly into the gastric lumen conferred protection against H. felis infection [11,17] and neutralized the toxic products of Helicobactor pylori [18].…”

E. coli Alpha Hemolysin and Properties

“…Representative examples include the tetanus toxoid (Xu-Amano et al, 1993), (Yamamoto et al, 1996), (Cheng et al, 1999), (Xu-Amano et al, 1994), the inactivated influenza virus (Hashigucci et al, 1996), (Tumpey et al, 2001), a recombinant urease from Helicobacter spp. (Lee et al, 1995), (Weltzin et al, 1997), (Lee, 2001), and the pneumococcal surface protein A from S. pneumoniae (Wu et al,1997). Many other examples have been reported, and all these studies clearly indicate that both LT and CT have significant potential for use as adjuvants for mucosally administered antigens.…”