Vaccination against Helicobacter pylori in non-human primate models and humans.
Several vaccination studies have been performed in monkeys and humans testing the feasibility of prophylactic and therapeutic immunizations against Helicobacter pylori. The monkey studies showed that immune responses were induced by oral vaccination with the mucosal adjuvant LT (Escherichia coli heat-labile enterotoxin), parenteral administration with a cationic lipid adjuvant, and by mucosal priming followed by parenteral boosts. Both prophylactic and therapeutic activities were demonstrated in monkeys, providing a strong impetus for human vaccine trials. Preliminary studies in humans were undertaken in order to identify a tolerable dose of LT adjuvant or to test the effectiveness of mutant atoxic LT adjuvants. The results from these preliminary studies suggest that native LT causes diarrhoea at doses required for adjuvanticity while a mutant LT does not. In one study in which infected human subjects were vaccinated with orally administered urease antigen with native LT, there was a modest reduction in the level of H. pylori gastric colonization. A second clinical study employing H. pylori whole cell antigen and a mutant LT in infected subjects showed immune responses and although the subjects remained infected, the study was not designed to measure reduction in H. pylori colonization. Recombinant Salmonella expressing urease and other H. pylori antigens have been effective in mice (see accompanying Frontlines Topic Review by John O. Nedrud [1]), but monkey studies are not possible because of host range restriction. Human trials of parenteral immunization, mucosal immunization with mutant LT and live Salmonella vectors are needed to fully assess the ability of vaccines to prevent or treat H. pylori infections.
Lee
C K
CK
Acambis, Inc., Cambridge, MA 02139, USA. cynthia.lee@acambis.com
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000008:administration & dosage; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000009:adverse effects; D001428:Bacterial Vaccines / Q000008:administration & dosage*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000008:administration & dosage / Q000009:adverse effects; D029968:Escherichia coli Proteins; D005544:Forecasting; D005767:Gastrointestinal Diseases / Q000517:prevention & control / Q000628:therapy; D000882:Haplorhini; D016481:Helicobacter Infections / Q000517:prevention & control* / Q000628:therapy; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D014510:Urease / Q000008:administration & dosage
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; C027538:heat-labile enterotoxin, E coli; D014510:Urease