Results are shown for samples obtained before immunization (0 week), 2 weeks following immunization (14 weeks), just prior to challenge (arrow), and at 4 and 11 weeks (IgG only) after challenge (18 and 25 weeks, respectively)

Results are shown for samples obtained before immunization (0 week), 2 weeks following immunization (14 weeks), just prior to challenge (arrow), and at 4 and 11 weeks (IgG only) after challenge (18 and 25 weeks, respectively). those infected will go on to develop either peptic ulcer or gastric adenocarcinoma, which is the second-most-common cause of cancer mortality worldwide. Therapy of requires the prolonged administration of several agents, and even under the best of circumstances it fails in 10 to 15% of cases. The growing development of antibiotic resistance further complicates the future of management (16). Immunization is an alternative strategy that may be useful as Pirmenol hydrochloride primary prevention and perhaps also as therapy for contamination. The early encouraging results obtained in the mouse model (4, 12, 13, 22, 27, 29) were confirmed by subsequent studies which showed that mice can be guarded from challenge by immunization with a variety of whole-cell or recombinant antigens (3, 14, 15, 26, 31). Most studies have utilized oral administration of recombinant urease, which has been shown to be effective as therapy and as primary prevention. Protection typically ranges from ca. 60 to 100%, depending on the particular adjuvant and challenge strain. More recently, parenteral administration of urease, together with a synthetic glycolipid adjuvant, has also been shown to be effective for primary prevention of (18). These promising results obtained in the mouse model have been only Pirmenol hydrochloride partially supported by recent studies in the rhesus monkey. Captive rhesus monkeys are naturally colonized with that is indistinguishable from that found in humans (5C7, 33) and therefore may represent a more appropriate test of vaccine efficacy than the mouse, which is not a natural host for or urease plus enterotoxin (LT) was not effective therapy for and prevented contamination in only a small percentage of naturally colonized animals that were challenged following antibiotic treatment (24). However, a reduced level of colonization was seen in vaccinated monkeys compared to sham controls. A subsequent study with antibiotic-treated monkeys found that all vaccinated animals as well as controls were infected following challenge, but again the colonization level was reduced in monkeys that received oral vaccine followed by a parenteral boost (23). These studies, however, differ from the anticipated use of a vaccine in humans because the animals were not immunologically naive to in very young animals, 69% of monkeys immunized with oral urease and E2F1 LT developed infection, compared with 93% of controls (8). However, the results are difficult to interpret because the initial absence of infection was documented only by serology, which is not sensitive for the detection of newly acquired infection. Unlike in the challenge experiments, the vaccine produced no reduction in bacterial colonization among the animals that became infected. Pirmenol hydrochloride We have developed a protocol for derivation of specific-pathogen (in SPF rhesus monkeys. MATERIALS AND METHODS Animals. Eleven newborn rhesus monkeys were taken from their dam within 24 h of birth and pair housed in temperature- and humidity-controlled incubators in the nursery. At approximately 1.5 years of age monkeys were examined for by serology, [14C]urea breath test, and histology and culture of gastric biopsies by using methods previously described (33). All 11 animals were free of and and were approved by the Research Advisory Committee of the California Regional Primate Research Center. Vaccine and adjuvant preparation. Vaccines and adjuvants were provided by OraVax (Cambridge, Mass.). Catalytically inactive but fully assembled urease apoenzyme was purified from containing either plasmid pORV214 (oral vaccine) or pORV273 (parenteral vaccine) by methods described previously (25). pORV273 is a proprietary construct identical to Pirmenol hydrochloride pORV214 except that the urease binding sites are substituted, and it was used to prepare parenteral vaccine for production rather than scientific reasons. There are no detectable antigenic differences between urease made from these two constructs. Urease for parenteral administration was purified by passing.