Immunization of rhesus monkeys with a mucosal prime, parenteral boost strategy protects against infection with Helicobacter pylori

Rhesus monkeys were immunized with recombinant Helicobacter pylori urease v accine given solely by the parenteral route or preceded by a priming dose g iven by the oral route. Two groups of monkeys received parenteral urease wi th either a synthetic glycolipid adjuvant (Bay) or aluminum hydroxide (alum ) as adjuvants, A third group of monkeys received a priming dose of oral ur ease given with the mucosal adjuvant LT (Escherichia coli heat labile enter otoxin), followed by parenterally administered booster doses of urease adso rbed to alum. Monkeys receiving placebo served as controls. The monkeys rec eived a total of 4 doses of vaccine with the first 3 doses given every 3 we eks and the last booster dose administered 14 weeks later. The monkeys were challenged orally with H. pylori one week after the last vaccine dose and euthanized 10 weeks after challenge, at which time, their stomachs were col lected for determination of bacterial colonization and histopathology, Monk eys primed with the oral vaccine and boosted with the parenteral vaccine sh owed a statistically significant reduction in bacterial colonization when c ompared to sham-immunized control animals (P = 0.05; Wilcoxon rank sums tes t), Monkeys receiving parenteral only regimes of urease plus Bay or alum sh owed no difference in bacterial colonization compared with sham-immunized c ontrols (P = 1.00 and P = 0.33, respectively). The mucosal prime-parenteral boost regime did not cause gastropathy, There was no difference in any of the 3 treatment groups with respect to gastric epithelial changes compared to control animals. There was also no difference in the type and extent of gastric inflammatory cell infiltrates between animals vaccinated by the muc osal prime-parenteral boost strategy and sham immunized controls. However, monkeys receiving the two parenteral-only regimens had slightly elevated ga stritis scores. (C) 1999 Elsevier Science Ltd. All rights reserved.