Helicobacter pylori Vaccine Development

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Helicobacter pylori Vaccine Development

• Catherine O. Johnson
• March 9, 2006

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Pathogen Background

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

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Requisite Nasty Pictures
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Nasty Pictures (2)
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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

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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

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Worldwide Prevalence of Infection
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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

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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

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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

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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

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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