Parasite Vaccines

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Parasite Vaccines
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Why Vaccinate?

• Have you been vaccinated?
• Against what?
• Why were you vaccinated?

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Antibody production
2o response
1o response
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Passive and Active immunity

• Passive
• Pre-formed antibodies injected into patient
• - E.g. anti-snake venom antibodies made in
  horses
• Give protection against disease
• Active
• Pathogen (e.g. virus) injected into patient
• Patients own immune system makes protective
  antibodies
• Vaccination

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Types of Immunity

• Cellular and Humoral immunity
• Cellular
• Cytotoxic T cells
• B cells Helper T cells
• Antigen presenting cells (macrophages)
• Humoral (soluble proteins)
• Antibodies (IgG, IgM, IgA, IgD, IgE)
• Cytokines
• Complement proteins

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What is a Vaccine?

• Pathogen (virus/bacterium/parasite or its
  components)
• injected into an animal/patient
• stimulates the animals immune system
• produces a protective cellular (cytotoxic T
  cell) or humoral (antibody) response against the
  pathogen

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Information Required to Produce a Vaccine

• Understand the of biology of pathogen
• - Determine most appropriate life cycle
• stage to target
• Understand immune mechanisms required to
  eliminate pathogen
• - Humoral (antibody) or
• - Cellular (cytotoxic T cell)

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Requirements forSuccessful Vaccine

• Effectiveness
• Must give protective levels of immunity
• At right place (e.g. mucosa)
• Right type-cytotoxic T cell or antibody
• For long enough
• ? Availability
• Easily produced in bulk

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Requirements forSuccessful Vaccine

• Stability
• - Stable under extreme climatic conditions
• - Refrigeration preferably not required
• Affordability
• - Western costs not practical in developing
• countries
• - Assistance from WHO and Intl. Foundations
• Safety
• - Not revert to pathogenic form

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Types of Vaccines

• Killed organisms
• Live attenuated organisms
• Subunit vaccines
• Synthetic peptide vaccines

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Killed Organisms

• Pathogen is killed/inactivated
• E.g. typhoid, cholera, poliomyelitis (Salk)
• Care should be taken not to destroy epitopes
• during killing (inactivation) process
• Immune response to these is generally poor

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Live Attenuated Organisms

• Organism is modified to mimic behaviour of
  original organism without causing disease
• Use strains not virulent in species vaccinated
  e.g. cowpox
• Modify growth conditions e.g. BCG bile to
  Mycoplasma tuberculosis
• Irradiation X-rays/UV or chemical treatment
• Virulence genes modified by genetic
  engineering-lower virulence in man
• Microbial vectors for genes of pathogens
• Viral DNA placed into DNA of virus carrier like
  vaccinia virus

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Advantages of LiveAttenuated Vaccines

• Larger and more sustained dose of
• immunogen possible
• Cytotoxic T-cell memory established
• Response occurs at site of natural
• infection
• - E.g. Sabin polio vaccine-oral vaccine
• induces persistent high levels of IgA (in
  mucosa)

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Problems WithAttenuated Vaccines

• Possible survival of infectious agent
• Difficult to obtain sufficient amounts of
• infective stage for commercial use
• Specialised storage requirements
• Ethical considerations - administering
• potentially infective organisms

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Subunit Vaccines

• Contain protective antigens
• - Purified components
• - Recombinant antigens
• - Naked gene therapy

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Subunit Vaccines

• Purified components
• Parasite protein(s)
• Adjuvant required (non-specifically
• stimulates immune system)
• Induce humoral (antibody) response
• Note Parasitic infections (intracellular)
  require
• cellular immune responses

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Subunit Vaccines

• Recombinant antigens
• - Gene coding for protective Ag synthesised
• - Inserted into appropriate vector
• - Expressed in yeast, bacterial, insect systems
• to produce large quantities of antigen
• E.g. Hepatitis B vaccine
• - Transgenic plants expressing protein
• vaccines under consideration

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Subunit Vaccines

• Naked gene therapy
• - Gene placed in DNA plasmid
• - Injected into muscle
• - Prolonged expression of protein
• - Generates antibody and cytotoxic T-cell
• responses
• - Easy and quick to prepare
• - No cold chain storage required
• - Cheap

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Synthetic PeptideVaccines

• EPITOPE SPECIFIC VACCINES
• Identify protective epitope in protein
• Synthesise peptide and use as vaccine
• Anti-peptide antibodies able to
• recognise and neutralise (?) pathogen

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Synthetic PeptideVaccines

• REQUIREMENTS
• B-cell epitope (for Ab production)
• Helper and cytotoxic T-cell epitopes
• (stimulates these cells)
• Efficient delivery system
• - Carrier protein
• - Lipopeptides
• - Liposomes
• - Biodegradable microspheres

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Synthetic PeptideVaccines

• ADVANTAGES
• Chemically defined, stable at ambient
• temperature and cheap to produce
• Possible contamination with infectious
• agents/cellular products eliminated
• Could be designed to elicit the required
• cellular and humoral response

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Synthetic PeptideVaccines

• LIMITATIONS
• Immune response relatively weak
• requires boosters
• Linear peptides may not mimic required
• confirmation in parent protein
• - Many neutralisation sites are discontinuous
• epitopes
• Carrier and adjuvant requirements

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Problems Remaining in ProducingParasite Vaccines

• Parasites are comparatively complex
• organisms
• Parasites have complex life cycles
• Key point Poor understanding of the immune
  mechanisms (cellular or humoral) required to
  eliminate parasite infections