Immunogenicity of Recombinant Helicobacter pylori Urease B Administered by Various Routes and with Different Adjuvants

Abstract

Because of the high prevalence of Helicobacter pylori infection and the morbidity and mortality associated to the disease, development of a preventive vaccine has become a priority. To this goal, we produced recombinant H. pylori urease B (rUreB) and tested its immunogenicity in BALB/c mice when administered as 3 doses (week 0, 4 and 6) by either parenteral (intramuscular) or mucosal routes (intragastric, intranasal, intrarectal) and with the use of various adjuvants (none, CpG, alum or Freund's). The intramuscular route was more immunogenic than any mucosal route; of the mucosas, only intranasal induced modest levels of serum IgG. All adjuvants improved the seroresponse to plain rUreB and, of them, Freund's and alum were equally good and better than CpG ODN 1826. Stool IgA was barely detected by any immunization strategy.

Expression and Antigenic Evaluation of Helicobacter pylori UreB Fragment

“…Helicobacter pylori is the main cause of chronic infection in gastric mucosa, affecting 50% of the world's population (2). Recently, H. pylori has been shown to cause other complications, such as gastric ulcers, duodenal inflammation, and gastritis (3,4). According to the literature, a considerable proportion of patients, infected with H. pylori, may not develop gastroduodenal diseases and could remain asymptomatic for a long period (2).…”

“…According to the literature, a considerable proportion of patients, infected with H. pylori, may not develop gastroduodenal diseases and could remain asymptomatic for a long period (2). On the other hand, long-term infections raise the risk of conditions such as adenocarcinoma and gastric lymphoma (4,5).…”

“…The mortality rate, associated with Helicobacter pylori infection, has been estimated at 1 case per 34 infected men and 1 case per 60 infected women (4,6).…”

“…Many enzymes reduce the acidity of the immediate environment of H. pylori by producing ammonia and carbonate from urea (4,6).…”

“…Selection of urease as an immunization target is based on the fact that membrane proteins often elicit an immune response (4,6,9).…”