1. H.Sidra Yasin (BIOT 412) Vaccines

2. 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

3. General Method to produce the vaccine

4. Vaccine composition Following are: Immunisation Department, Centre for Infections

5. Modifiers of vaccines

6. Adjuvants • Boosters Modifiers of vaccines

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

8. Freund’s Adjuvant • Aluminum Hydroxide • Aluminum Phosphate (Alum) Types

9. Boosters • Periodic “booster” administration must be given in order to strengthen and lengthen the duration of immunity

10. Routs of administration

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

12. Types of vaccines

13. 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

14. Traditional vaccines

15. 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

16. 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

17. 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

18. Inactivated vaccines

19. 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

20. 2.Fractional

21. 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

22. 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

23. pure cell wall polysaccharide from bacteria Polysaccharide based; pure

24. Polysaccharide linked to a carrier protein • More potent • lacks long term immunological memory • Protect against: • Hib • Pneumococcal diseases • Tetanus • Diphtheria Polysaccharide based; conjugate

25. 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

26. 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

27. 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

28. So!!!

29. Recombinant vaccines

30. Subunit Vaccines • Peptide vaccines • DNA Vaccines • Vector Vaccines Types

31. 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

32. With carrier proteins

33. 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.

34. 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

35. 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

36. Human Diseases for Which Recombinant Vaccines Are Currently Being Developed

37. Vaccine Production methods

38. 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

39. 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.

40. 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.

41. 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.

42. Summary!!!

43. Thank you!