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H.Sidra Yasin (BIOT 412). Vaccines. 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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H.Sidra Yasin (BIOT 412) Vaccines
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 Learning objectives
Vaccine composition Following are: Immunisation Department, Centre for Infections
Adjuvants • Boosters Modifiers of vaccines
Chemical substance that can be added to a vaccine in order to enhance the immune response to the vaccine. Adjuvants
Freund’s Adjuvant • Aluminum Hydroxide • Aluminum Phosphate (Alum) Types
Boosters • Periodic “booster” administration must be given in order to strengthen and lengthen the duration of immunity
Routes • Intradermal administration. • Three types are; intravenous intramuscular subcutaneous. • Oral administration. • Vaccine is usually given in liquid form. • Foods • Intranasal administration.
Traditional Recombinant vaccines 1. Types A. Inactivated B. Live C. Attenuated 2. Pathogens A. Bacteria B. Virus C. Parasites • Subunit Vaccines • peptide vaccines • Attenuated Vaccines • Vector Vaccines • Bacterial Antigen Delivery Systems Types of vaccines
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. Live, Attenuated Vccines
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 Live, Attenuated 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 Inactivated Vaccines
actual pathogen • killed, either by a heat treatment or chemically • Salk vaccine for polio, which utilizes whole polioviruses that have been inactivated by formaldehyde. 1.whole
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 Protein based; Toxoids
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) Protein based; Subunit
pure cell wall polysaccharide from bacteria Polysaccharide based; pure
Polysaccharide linked to a carrier protein • More potent • lacks long term immunological memory • Protect against: • Hib • Pneumococcal diseases • Tetanus • Diphtheria Polysaccharide based; conjugate
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… Inactivated vaccines
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 Possible Limitations of Traditional Vaccine Production
Delete virulence genes • Use live nonpathogenic carriers for immunization (unrelated pathogenic agent) • Clone antigenic determinants into alternative host • Address autoimmune system response/problems New Strategies
Subunit Vaccines • Peptide vaccines • DNA Vaccines • Vector Vaccines Types
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 Peptide vaccines
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.
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 Genetic Immunization
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. Chimeric Vaccines
Human Diseases for Which Recombinant Vaccines Are Currently Being Developed
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. Vaccine Production Methods
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.
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.
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.