Vaccines

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Vaccines

• H.Sidra Yasin (BIOT 412)

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Learning objectives

• What are the Methods to produce the vaccines
• How we can modify the Vaccines
• What are the Routs of administration of vaccines
• What are the Types of vaccines
• What is Reverse vaccinology and its purpose
• Summary of all topics with conclusion

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General Method to produce the vaccine
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Vaccine composition

• Following are

Component Purpose Example
Adjuvants enhance the immune response to a vaccine aluminium salts
Preservatives prevent bacterial or fungal contamination of vaccine thiomersal
Additives stabilise vaccines from adverse conditions such as freeze-drying or heat, thereby maintaining a vaccines potency gelatine
Residuals from manufacturing process Inactivating agents Antibiotics - prevent bacterial contamination during manufacturing process Egg proteins- some vaccine viruses are grown in chick embryo cells Yeast proteins formaldehyde neomycin, streptomycin, polymyxin B influenza, yellow fever HepB vaccine
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Modifiers of vaccines
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Modifiers of vaccines

• Adjuvants
• Boosters

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Adjuvants

• Chemical substance that can be added to a vaccine
  in order to enhance the immune response to the
  vaccine.

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Types

1. Freunds Adjuvant
2. Aluminum Hydroxide
3. Aluminum Phosphate (Alum)

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Boosters

• Periodic booster administration must be given
  in order to strengthen and lengthen the duration
  of immunity

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Routs of administration
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Routes

• Intradermal administration.
• Three types are intravenous
• intramuscular subcutaneous.
• Oral administration.
• Vaccine is usually given in liquid form.
• Foods
• Intranasal administration.

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Types of vaccines
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Types of vaccines

• Traditional

• Recombinant vaccines

• 1. Types
• A. Inactivated
• B. Live
• C. Attenuated
• 2. Pathogens
• A. Bacteria
• B. Virus
• C. Parasites

1. Subunit Vaccines
2. peptide vaccines
3. Attenuated Vaccines
4. Vector Vaccines
5. Bacterial Antigen Delivery Systems

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Traditional vaccines
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Live, Attenuated Vccines

• Act like natural infection
• Live, but weakened, viruses or bacteria
• Altered organisms, either genetically or
  chemically but non pathogenic
• Example
• Attenuated virus vaccine for yellow fever,
  which utilizes the YF17D strain, a weakened form
  of the wild virus.

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Live, Attenuated vaccines

• Advantages

• Disadvantages

• Single dose sufficient to induce long-lasting
  immunity
• Strong immune response
• Local and systemic immunity
• Others
• Polio and Adeno

• Potential to revert to virulence
• Contraindicated in immunosuppressed patients
• Interference by viruses or vaccines and passive
  antibody
• Poor stability
• Potential for contamination

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Inactivated Vaccines

• Either
• Suspensions of whole intact killed organisms
• e.g. whole cell Pertussis, Influenza, Rabies,
  HepA
• Or
• Acellular and sub-unit vaccines
• e.g. Acellular Pertussis vaccine contains
  between 2-5 components of the whole cell
  Pertussis bacteria

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Inactivated vaccines
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1.whole

• actual pathogen
• killed, either by a heat treatment or chemically
• Salk vaccine for polio, which utilizes whole
  polioviruses that have been inactivated by
  formaldehyde.

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2.Fractional
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Protein based Toxoids

• Stimulates the antibody mediated response
• Exotoxins
• Toxoids are vaccines which consist of exotoxins
• Immunity against the toxins, but not necessarily
  the bacteria that produce the toxins.
• Examples
• Botulinum antitoxen
• Diphtheria antitoxen
• Pertusis
• Tetanus toxoids

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Protein based Subunit

• Pathogenic agent
• Use components of pathogenic organism instead of
  whole organism
• Advantage no extraneous pathogenic particles i.e
  DNA
• Disadvantage Costly
• Examples
• HSV
• Method of production
• Tuberculosis
• Foot -and-Mouth Disease virus (FMDV)

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Polysaccharide based pure

• pure cell wall polysaccharide from bacteria

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Polysaccharide based conjugate

• Polysaccharide linked to a carrier protein
• More potent
• lacks long term immunological memory
• Protect against
• Hib
• Pneumococcal diseases
• Tetanus
• Diphtheria

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Inactivated vaccines

• Advantages

• Disadvantages

• Stable
• Constituents clearly defined
• Gives sufficient humoral immunity if boosters
  given
• No mutation or reversion
• Can be used with immuno-deficient patients

• Many vaccinees do not raise immunity
• Shorter lasting immunity
• Boosters needed
• Need several doses
• Adjuvant needed
• Failure in inactivation and immunization with
  virulent viruses
• Others

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Possible Limitations of Traditional Vaccine
Production

• Not all infectious agents can be grown in culture
• Animal/human cell culture expensive if needed
• Yield of viruses from cultures can be low
• Safety precautions for culture of live agents
• Insufficient killing/attenuation of agents
• Reversion of attenuated agents
• Traditional vaccines are less diverse

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New Strategies

• Delete virulence genes
• Use live nonpathogenic carriers for immunization
  (unrelated pathogenic agent)
• Clone antigenic determinants into alternative
  host
• Address autoimmune system response/problems

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So!!!
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Recombinant vaccines
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Types

1. Subunit Vaccines
2. Peptide vaccines
3. DNA Vaccines
4. Vector Vaccines

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Peptide vaccines

• Use discrete portion (domain) of a surface
  protein as Vaccine.
• These domains are epitopes
• antigenic determinants
• are recognized by antibodies
• Use highly immunogenic carrier molecule

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With carrier proteins
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DNA Vaccines

• DNA vaccines consist of plasmids that contains
  genes for certain types of antigens.
• Once administered, the plasmid is taken up by the
  target cell and the genes are expressed.
• The cell then either excretes the antigen or
  displays it on an MHC-I molecule.

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Genetic Immunization

• Delivery of a gene for the antigen to a host
  organism
• Use vector containing cDNA from viral protein/
• eukaryotic promoter
• Inject into muscle

• POTENTIAL
• Eliminates purification of antigen
• Protein is modified post-translationally

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Chimeric Vaccines

• Consist of attenuated viruses have been
  engineered to carry antigens from multiple types
  of pathogens.
• The yellow fever vaccine has been engineered to
  carry antigens from HIV, different types of
  bacteria, malaria, even cancer.
• immunity against several different diseases with
  one administration.

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Human Diseases for Which Recombinant Vaccines Are
Currently Being Developed
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Vaccine Production methods
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Vaccine Production Methods

• Manufacturing strategies
• In-vivo
• In-vitro
• Chemical Synthesis
• Some vaccines can be produced using any one of
  the three methods while for other vaccines, only
  one method will work.

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In-Vitro

• Here, using recombinant DNA technology, vaccines
  can be produced in yeast cultures, bacterial
  cultures, or cell cultures.
• Recombinant vaccines, such as chimeric and
  Attenuated virus/bacteria vaccines, are produced
  in this manor.

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In-Vivo

• Embryonated Chicken eggs are commonly used as in
  producing flu vaccines.
• Vaccines, like anti-idiotype, can also be
  produced in lab animals, such as mice.
• There are even some species of plant, such as
  bananas, that have been genetically engineered to
  produce a vaccine.

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Chemical Synthesis

• Produced in a lab.
• Vaccines that utilize synthetic peptides as well
  as conjugated lipids and polysaccharides
• Used in combination with either in-vivo or
  in-vitro production.

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Summary!!!
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Thank you!
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