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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

Helicobacter pylori Vaccine Development

Catherine O. Johnson

March 9, 2006

pathogen background
Pathogen Background
  • Gram negative bacteria
  • Colonizes the human gastrointestinal tract and stomach
  • Oral-Oral or Oral-Fecal routes of person-to-person transmission
mechanism of infection
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
burden of disease
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
treatment
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
vaccine development
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
genetic diversity of h pylori
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
vaccine delivery
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
clinical trial of vaccine
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