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 vaccine given solely by the parenteral route or preceded by a priming dose given by the oral route. Two groups of monkeys received parenteral urease with either a synthetic glycolipid adjuvant (Bay) or aluminum hydroxide (alum) as adjuvants. A third group of monkeys received a priming dose of oral urease given with the mucosal adjuvant LT (Escherichia coli heat labile enterotoxin), followed by parenterally administered booster doses of urease adsorbed to alum. Monkeys receiving placebo served as controls. The monkeys received a total of 4 doses of vaccine with the first 3 doses given every 3 weeks 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 collected for determination of bacterial colonization and histopathology. Monkeys primed with the oral vaccine and boosted with the parenteral vaccine showed a statistically significant reduction in bacterial colonization when compared to sham-immunized control animals (P = 0.05; Wilcoxon rank sums test). Monkeys receiving parenteral only regimes of urease plus Bay or alum showed no difference in bacterial colonization compared with sham-immunized controls (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 mucosal prime-parenteral boost strategy and sham immunized controls. However, monkeys receiving the two parenteral-only regimens had slightly elevated gastritis scores.
Lee
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CK
OraVax Inc., Cambridge, MA 02139, USA. clee@oravax.com
Soike
K
K
Giannasca
P
P
Hill
J
J
Weltzin
R
R
Kleanthous
H
H
Blanchard
J
J
Monath
T P
TP
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000284:Administration, Oral; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006017:Glycolipids / Q000276:immunology; D016481:Helicobacter Infections / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control / Q000662:veterinary*; D016480:Helicobacter pylori / Q000254:growth & development / Q000276:immunology*; D007117:Immunization, Secondary; D007263:Infusions, Parenteral; D008253:Macaca mulatta; D008992:Monkey Diseases / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control; D011897:Random Allocation; D011994:Recombinant Proteins / Q000276:immunology; D014510:Urease / Q000276:immunology
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D001428:Bacterial Vaccines; D006017:Glycolipids; D011994:Recombinant Proteins; C073836:Bay-R 1005; C041524:aluminum sulfate; D014510:Urease