Parasite Vaccines'

1
Parasite Vaccines.

• Jo Hamilton
• Parasitology
• BS31820

2
Objectives and learning outcomes.

• Why develop parasite vaccines?
• What we need to know to develop parasite vaccine?
• Why parasite vaccine success limited?
• Types of vaccines advantages / disadvantages?
• Specific examples of parasite vaccines in
  clinical trial.

3
What does a vaccine do ?

• Stimulates normal protective immune response of
  host to fight invading pathogen.

4
Why develop parasite vaccines?

• Part of a control programme
• ? Advantages over drugs disease prevention
  strategies.
• History of success in other diseases
• ? anti-viral anti-bacterial vaccines.

5
What knowledge is needed to produce a vaccine ?

• 1. Understand lifecycle of parasite
• ? find best target stage.
• 2. Understand immune mechanisms stimulated by
  parasite.
• ? humoral /cellular response ?

6
What does a vaccine need to do to work ?

• Antigens must produce protective
• response ? not stimulate non-protective
  mechanisms.
• Vaccine must stimulate good response
• ? without adjuvant is best.
• Good level of protection without boosting
• ? using simple delivery system.

7
Vaccine success stories.

• Vaccines available for-
• Diphtheria
• Tetanus
• Measles
• Mumps
• Rubella
• Polio
• Hepatitis B etc.  

8
Success with commercial parasite vaccines ?

• Conventional approaches
• Dictyocaulus irradiated larval vaccine.
• (Dictol)
• Theileria attenuated live vaccines.

9
Success with commercial parasite vaccines ?

• Molecular approaches
• Ticks recombinant antigen (TickGARD)
• Sheep tapeworm recombinant antigen (not
  available now).

10
Why limited success in parasite vaccine
development ?

• Parasites avoid, deflect confuse host immune
  system.
• Right parasite antigens not identified yet
  complicated life cycles.
• (maybe 20,000 proteins in nematodes).
• Protective host responses not understood in
• target species multi-responses
• (most research in rodent models)

11
Types of Vaccines.

• 1. Whole pathogens killed prior to inoculation.
• 2. Attenuated live or low virulence vaccines.
• 3. Protein Subunit vaccines.
• ? Natural tissue purified proteins.
• ? Recombinant protein antigens.
• ? Chemical small peptide vaccines.
• 4. Nucleic acid vaccines.

12
How does molecular biology biochemistry help
subunit vaccine production ?

• Identify protective antigens
• ? Screening cDNA libraries protein
• arrays with infection sera.
• Cloning gene encoding antigen.
• Production recombinant form of antigen.

13
Recombinant Adult Hookworm Secreted Protein.
HUMAN HOOKWORM VACCINE INITIATIVE The Albert B.
Sabin Vaccine Institute.
14
Recombinant vs. Natural Subunit Vaccines.

• Advantages of recombinant
• Produced cheaply consistently
  in
  bacteria, yeast or cell lines.
• Natural protein isolation - animals
  extraextraction procedures.
• Natural protein antigens often impure.

15
Recombinant vs. Natural Subunit Vaccines.

• Disadvantages of recombinants
• Parasite populations might be polymorphic
• ? vaccine ineffective against some strains.
• Simple recombinant might not stimulate all
• required immune components
• e.g. immunogenic carbohydrate wrongly
  processed in production.

16
Synthetic Peptide Vaccines.

• Product chemically defined.
• Stable at ambient temperatures.
• No infectious agents or other proteins in
  formulation.
• Designed to stimulate correct immune response.

17
What is a DNA Based Vaccine ?

• Gene encoding antigen cloned into DNA carrier
  (plasmid) containing host expression trigger
  (promoter).
• ?
• Vaccinate host with plasmid
• ?
• Parasite DNA produced by host cells
• ?
• Induction of protective immune response

18
Potential Advantages of DNA Vaccines ?

• All produced by simple generic technique.
• Given for multiple diseases in one injection.
• Long lived responses.
• Extremely stable fridges not needed
• ? transported dried or in solution.

19
How would a candidate vaccine reach advanced
human trials?

• Consistent protection levels in animal
• models.
• Free from gross tissue side-effects.
• Pass recognized toxicity tests - animal
• models human phase I.
• Good production record - low costs, stable
  formulation.

20
Latest news on recombinant subunit vaccines.

• Schistosomiasis
• 4 recombinants in Phase I / Phase
• II human trials (3 internal proteins?).
• Some only reduce egg output not
• worm burden decreasing pathology.

21
Latest news on recombinant subunit vaccines.

• Malaria
• Pre-erythrocyte antigens
• Coat protein up to 80 protection in
• phase II. RTS,S/SBAS2 now in field trials.
• Asexual blood stage antigens
• AMA 1 - Combination 3 antigens, 47 protection
• in phase II. But problems with scale up.
• Latest - PfCP-2 combination 2 ags -phase I 2003.

22
Latest news on recombinant subunit vaccines.

• Hydatid disease
• (Melbourne University WHO)
• Trials with molecular vaccine based on egg
  protein in progress in South America Asia.

23
Latest news on recombinant subunit vaccines.

• Leishmaniasis
• 1st Generation killed whole parasites- human
  trials in
• Middle East, Africa Latin America
• Mean 55 protection over 2 years in boys only
  ?
• 2nd Generation 10 recombinants tested in mice
  including
• with cytokine adjuvants
• Inconclusive protection antigens unstable ?
• Latest Hybrid recombinant vaccine (portions 3
  proteins) mono-phosphoryl lipid A Phase 1
  safety/tolerability late 2002.

24
Summary I.

• Vaccine candidates must produce good protective
  immune response.
• Already successful vaccines against bacteria
  viruses.
• Parasites evade, modulate and manipulate host
  immune system.
• Some commercial veterinary vaccines.

25
Summary II.

• Vaccine types
• Whole killed pathogens.
• Live attenuated pathogens.
• Pathogen protein subunits.
• Parasite Nucleic Acids.
• Some vaccine candidates in clinical trials for
• Schistosomiasis, Malaria, Hydatid disease
  Leishmaniasis.

26
Suggested reading.

• Please see handout for details of latest parasite
  vaccine developments.
• Other information on earlier vaccine developments
  can be found at
• http//www.who.int/tdr/publications/publications/
  default.htm

27
Next lecture.

• Review, compare contrast vertebrate
  invertebrate immunity.
• Basis for immune evasion lectures.