Vaccine
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The document provides an overview of the history and development of vaccines. It discusses key events like Jenner's development of the smallpox vaccine in 1796 and the eradication of smallpox. It describes different types of vaccines including live-attenuated, inactivated, toxoid, subunit, conjugate, and DNA vaccines. The mechanisms of how vaccines work and produce immunity are also explained. The document traces the evolution of vaccines from whole organism approaches to modern techniques like recombinant DNA technology.
Vaccine
- 1. VACCINES A JOURNEY FROM JENNER TO GENES
- 2. HISTORICAL PERSPECTIVES 2 Jenner 1796 : Cowpox • 1800’s Compulsory childhood vaccination • 1930’s Last natural UK case • 1940’s last natural US case • 1958 WHO program • October 1977: Last case (Somalia)
- 3. Immunization Immunisation is the process of conferring increased resistance (or decreased susceptibility) to infection
- 4. Active Vs Passive Immunization Active immunization Can be achieved through natural infection by a microorganism or it can be acquired artificially through the administration of vaccines Antibodies produced in response to an infection e.g. natural measles virus Antibodies produced in response to a vaccine (live, inactivated or toxoid) Individuals make their own antibodies
- 5. Active Vs Passive Immunization Passive Immunity Individual gains antibodies from another who has produced them Transfer of maternal antibodies through the placenta or in breast milk Administration of antibodies collected from actively immune humans or animals e.g. varicella zoster immunoglobulin VZIG
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- 7. What is a Vaccine? A preparation of the causative agent of a disease, specially treated for use in vaccination, in order to induce or increase immunity Typically contains an agent that resembles a disease-causing microorganism, and is often made from Weakened or killed microorganisms or subunits (purified protein subunits, polysaccharides).
- 8. What is a Vaccine? Based on 2 key elements of adaptive immunity: Specificity and Memory Stimulation of an individual’s own immune system to produce antibodies by administration of a vaccine
- 9. Active Immunization through designing Vaccines 9 Before designing any vaccine, two things should be considered: Activation of humoral and cell mediated immune response shown by a particular antigen Development of immunologic memory by the particular antigen
- 10. The Mechanism of a Vaccine In an ideal scenario, whenever a vaccine is first administered, it is phagocytized by an antigen presenting cell. Recent research suggest that it is particularly important that the vaccine be taken up by a dendritic cell. This is because dendritic cells play a key role in activating T cells, which become helper T cells
- 11. From there, the activated Th cells goes on to activate mature B-cells. These activated B-cells divides into two cell types, antibody- producing plasma cells and, most importantly, memory B cells. The Mechanism of a Vaccine
- 12. Importance of Secondary Immune Response During the secondary immune response, the body mounts a quicker, more robust attack on the pathogen. Thus, the pathogen is cleared from the body before it has the chance to cause an infection.
- 13. Adjuvants An adjuvant is a chemical substance that can be added to a vaccine in order to enhance the immune response to the vaccine. There are three types of adjuvants.
- 14. Adjuants Aluminum Hydroxide and Aluminum Phosphate (Alum) Alum is an inorganic salt that binds to proteins and causes them to precipitate. Whenever the alum/vaccine complex is injected into the body, it slowly dissolves, releasing the vaccine. Bacterial extracts can be added, which enhances the immune response. Alum is the only adjuvant approved for use in humans.
- 15. Adjuants Freund’s Adjuvant In Freund’s adjuvant, the vaccine is suspended in oil droplets. When injected into the body, the vaccine slowly diffuses out of the oil drop. Bacterial antigens can be added in order to enhance the immune response. Not used in humans because of risk of severe inflammation.
- 16. Routes of Administration There are three different routes of administration: Intradermal administration. Three types are intravenous, intramuscular, and subcutaneous. Oral administration. Vaccine is usually given in liquid form. Foods, such as tomatoes, have been engineered to produce a vaccine. Intranasal administration.
- 17. Boosters For most vaccines, the immunity against a particular pathogen has a tendency to wear off over time. In this case, a periodic “booster” administration must be given in order to strengthen and lengthen the duration of immunity.
- 18. Active immunization by artificial means can be achieved by:18 Attenuated organisms (avirulent) Inactivated organisms (killed) Purified microbial macromolecules Cloned microbial antigens Synthetic peptides Anti-idiotype antibodies Multivalent complexes
- 19. Types of Vaccines 19 Live-attenuated Inactivated Toxoid Subunit Conjugate Combination Innovative Edible
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- 21. Live-attenuated Vaccine 21 Oral Polio Vaccine (Sabin) MMR (measles, mumps and rubella) Varicella BCG Rotavirus Oral typhoid etc.
- 22. Advantages of Attenuated Vaccines 22 • •Raises immune response to all protective antigens. • More durable immunity • Low cost • Quick immunity in majority of vaccinees • In case of polio and adeno vaccines, easy administration • Easy transport in field •Disadvantages of Attenuated Vaccines Mutation; reversion to virulence (often frequent)
- 23. The Milestone 23
- 24. Inactivated vaccines The bacteria or virus is completely killed using a chemical, usually formaldehyde Examples hepatitis A hepatitis B poliovirus (Salk) influenza 24
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- 26. 26 Advantages of inactivated vaccines Gives sufficient humoral immunity if boosters given • No mutation or reversio Disadvantages of inactivated vaccines • Many vaccinees do not raise immunity • Boosters needed • No local immunity (important) • Higher cost • Shortage of monkeys (polio) • Failure in inactivation and immunization with virulent virus
- 27. Vaccines from whole organisms Many of the currently used vaccines to date consist of inactivated or live but attenuated bacterial cells or virus particles Bacterial cells Plague , pertusis, cholera Inactivated Tuberculosis Attenuated BCG Viral particals Influenza , rubella virus Inactivated Polio (Salk) Inactivated Polio (Sabin) Attenuated Yellow fever Attenuated
- 28. Toxoid Vaccines Pathogenic toxin is modified to harmless toxoid Examples of Toxoid-based vaccines include tetanus and diphtheria 28
- 29. Attenuated Vs Inactivated Vaccines Attenuated Inactivated Method of production: Virulent strain grown under Virulence is inactivated by adverse culture conditions chemical treatment or by prolonged growth in unnatural radiation host or passage through different unnatural hosts Requirement of booster dose: Generally single booster dose Multiple booster doses is required are required Stability: Less stable More stable and resistant to natural temperature
- 30. Attenuated Vs Inactivated Vaccines Type of host Immune responses: Produce both cell mediated Mainly produces and humoral immune response humoral response Tendency to revert: May revert to original virulent Does not revert to virulent strain by recombination virulent form with wild type strain or reverse mutation Attenuated Inactivated
- 31. Subunit Vaccines • Risks associated with attenuated or killed whole vaccines can be avoided by subunit vaccines • Consist of specific, purified macromolecules derived pathogens 31
- 32. Subunit Vaccines 32 Protein subunit (toxoid)- diphteria, tetanus Bacterial polysaccharide- S. pneumoniae, Nisseria meningitidis Viral glycoproteins- Herpes simplex virus glycoprotein D Synthetic peptides produced from active epitopes of antigen are used as vaccines. Synthetic peptide vaccines for HIV, influenza, diphtheria toxin, hepatitis B virus and malaria parasite are currently being evaluated for their efficacy Not very successful as peptides are not as immunogenic as proteins
- 33. Subunit Vaccines Recombinant pathogen proteins- Gene coding any immunogenic protein cloned by recombinant DNA technology E.g. hepatitis Bs Ag gene cloned in yeast
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- 35. Recombinant Vectors Vaccines Attenuated viruses and bacteria serve as vectors Genes encoding major antigens of virulent pathogens can be introduced into these Wide range of organisms used as vectors: vaccinia virus, attenuated polio virus, canary pox virus, adenovirus, BCG strain of Mycobacterium bovis
- 36. The Hierarchy of Vaccines First generation vaccines are whole-organism vaccines – either live and weakened, or killed forms. The so-called second generation vaccines are subunit vaccines, consisting of defined protein antigens (such as tetanus or diphtheria toxoid) or recombinant protein components (such as the hepatitis B surface antigen). DNA vaccines are third generation vaccines
- 37. DNA Vaccines - The Third Generation Vaccines 37 • 1796 Jenner: wild type animal-adapted virus • 1800’s Pasteur: Attenuated virus • 1996 DNA vaccines
- 38. DNA Vaccines Made up of plasmid that has been genetically engineered to produce one or two specific proteins (antigens) from a pathogen. The vaccine DNA is injected into the cells of the body, where the "inner machinery" of the host cells "reads" the DNA and converts it into pathogenic proteins. Because these proteins are recognised as foreign, when they are processed by the host cells and displayed on their surface, the immune system is alerted, which then triggers a range of immune
- 39. Applications of DNA Vaccines DNA vaccines are in their early phase of clinical trials. There are no DNA vaccines in market at present. At present human trials are under way for malaria, influenza, AIDS, Ebola and Herpes.
- 40. Advantages of DNA Vaccines 40 Plasmids are easily manufactured in large amounts DNA is very stable DNA resists temperature extremes so storage and transport are straight forward. Refrigeration is not required Stable for storage Elicit both humoral & cell mediated immunity Focused on Antigen of interest Long term immunity
- 41. Disadvantages of DNA Vaccines Limited to protein immunogen only Extended immunostimulation leads to chronic inflammation Plasmid used is resistance to antibiotics for selection. Can raise the resistance to same antibiotic in the host
- 42. Conjugate Vaccines Certain bacteria have polysaccharide outer coats that are poorly immunogenic (T independent Ags) By linking these outer coats to proteins (e.g. toxiods), the immune system can be led to recognize the polysaccharide as if it were a protein antigen Haemophilus influenzae type B vaccine 42
- 43. Combination vaccines 43 DTP - Combination vaccine prevents three diseases in one shot Diphtheria, Tetanus (lockjaw), Pertussis (whooping cough) MMR Measles, Mumps, Rubella
- 44. Edible vaccines 44 Antigens or antibodies expressed in plants Oral administration Cheaper Exhibit good genetic stability Do not require special storage conditions Since syringes and needles are not used, chances of infection are also less
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- 46. Anti-idiotype vaccines Idiotype- unique amino acid sequence of V domain of a given Ab – Ag binding site as well as antigenic determinant Generation of an effective immune response to a dangerous pathogen without exposing the individual to any form of pathogen as vaccine It is known as anti-idiotype antibodies Vaccines of this type have been developed against pathogens of viral, bacterial or parasitic type
- 47. 47 antibody Anti-idiotype vaccine epitope Antibody with epitope binding site Virus Anti-idiotype vaccines Anti-idiotype vaccines
- 48. 48 antibody Make antibody against antibody idiotype Anti- idiotype antibody Anti-idiotype antibody mimics the epitope Anti-idiotype vaccines
- 49. 49 Anti-anti-idiotype antibody Anti-idiotype antibody Use anti-idiotype antibody as injectable vaccine Antibody to anti-idiotype antibody Binds and neutralizes virus Anti-idiotype antibody Anti-anti-idiotype antibody Anti-anti-idiotype antibody Use as vaccine
- 51. Why aren't vaccines available for all diseases ?51 The procedure for developing a vaccine is time taking and very expensive Vaccines are prioritized in following order: Vaccines that fight diseases that cause the most deaths and damage, like meningitis Vaccines that prevent severe diseases like measles and influenza Vaccines, like the one for rotavirus, that prevent significant suffering Companies must get significant return on investment Some viruses mutate so quickly that traditional vaccines are ineffective. A prime example is the HIV/AIDS virus