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Helicobacter pylori Vaccine Development

Helicobacter pylori Vaccine Development. Catherine O. Johnson March 9, 2006. Pathogen Background. Gram negative bacteria Colonizes the human gastrointestinal tract and stomach Oral-Oral or Oral-Fecal routes of person-to-person transmission. Requisite Nasty Pictures. Nasty Pictures (2).

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Helicobacter pylori Vaccine Development

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  1. Helicobacter pylori Vaccine Development Catherine O. Johnson March 9, 2006

  2. Pathogen Background • Gram negative bacteria • Colonizes the human gastrointestinal tract and stomach • Oral-Oral or Oral-Fecal routes of person-to-person transmission

  3. Requisite Nasty Pictures

  4. Nasty Pictures (2)

  5. Mechanism of Infection • H. pylori is able to establish long-term infection in most individuals • Colonizes the mucus layer of the stomach lumen • Goes through adherent and non-adherent phases • Mechanism used to evade host defenses is not completely understood • Able to modulate host immune system to favor a TH1-type inflammatory response; able to specifically modulate the immune responses that would clear the bacteria • Extensive intrastrain and interstrain diversity • Genetic variation in hosts

  6. Burden of Disease • Most of the time, infected individuals are asymptomatic • 15-20% of infected individuals will develop severe gastrointestinal disease • Gastric tumors (particularly stomach body) • Peptic ulcers & active gastritis • Approximately 50% of the global population is infected with H. pylori • Higher rates in those of lower SES status • 80-90% of persons living in developing countries are infected by early adulthood

  7. Worldwide Prevalence of Infection

  8. Treatment • Triple Therapy • Proton pump inhibitor, amoxicillin and clarithromycin • Dosed 2 times per day for 1 week • Results in eradication of the organism in >80% of individuals • Does not prevent recolonization; antibiotic resistance is becoming problematic

  9. Vaccine Development • Interest in both preventive and therapeutic vaccines • Relatively good results in animal models • Problems with extending vaccines to human subjects • Multiple doses required; incomplete protection • Route of immunization: oral, rectal, intranasal • Genetic diversity of the organism

  10. Genetic Diversity of H. pylori • Most genetically diverse bacterial species • Strains differ in • Genome size • Gene order • Genetic content • Allelic profile • Associations between specific strains and increased incidence of severe sequelae • Cag pathogenicity island • Specific VacA cytotoxin alleles

  11. Vaccine Delivery • Difficult to generate an immunologic response in the stomach/gut with a systemic inoculation • Small studies have shown results with oral vaccines • Rectal, intranasal, intrajejunal vaccines are also being explored

  12. Clinical Trial of Vaccine • Trial of an oral therapeutic vaccine • Four doses of either 20, 60, or 180mg of recombinant H. pylori urease was given to infected subjects • Trial demonstrated immunogenicity of the vaccine; however a high proportion of the subjects reported diarrhea

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