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VACCINES

Copyright © 2007 by W. H. Freeman and Company

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Vaccination, or intentional exposure to forms of a pathogen that do not cause disease (a vaccine) �

Edward Jenner and Louis Pasteur�

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Properties of Ideal vaccine

  • Affordable worldwide
  • Heat stable
  • Effective after a single dose
  • Applicable to a number of diseases
  • Administered by a mucosal route
  • Suitable for administration early in life �

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Developing a vaccine

  • Lots of research
      • Time consuming, costly
      • Idea is to isolate a component of the organism that proves to be immunogenic….sometimes not possible
  • Human trials are strictly regulated
  • Might have vaccine developed but there might be adverse side effects – can’t be used…

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  • Immunity can be achieved by active or passive immunization
      • Passive – transfer of preformed antibodies
          • Maternal antibodies to fetus
          • Antibody therapy for bites, immunodeficiency
      • Active – long term protection, immunologic memory, actual exposure
          • Coming into contact with any foreign substance
          • vaccines

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The Immune System and Passive Immunization

  • The transfer of antibodies will not trigger the immune system

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  • There is NO presence of memory cells

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  • Risks are included
      • Recognition of the immunoglobulin epitope by self immunoglobluin paratopes
      • Some individuals produce IgE molecules specific for passive antibody, leading to mast cell degranulation
      • Some individuals produce IgG or IgM molecules specific for passive antibody, leading to hypersensitive reactions

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  • There is a chance of side effects in small # of population
      • That is the case with any treatment/drug
      • However, if the benefits to the population out-weigh the risk of side effects, vaccines must be used to protect the majority of the population
      • HERD IMMUNITY

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Herd Immunity

  • Factors affecting herd immunity
    • Environmental Factors: crowded conditions, seasonal variations

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    • Strength of Individual’s Immune System

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    • Infectiousness of Disease: greater the risk of infection, the higher percentage of people need vaccines to attain herd immunity

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  • When enough people are vaccinated, chance of germ infecting the non-immunized population is small

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  • Can lead to disappearance of diseases (smallpox)
    • Vaccination no longer necessary

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Designing Effective Vaccine

  • Protective immunity must be achieved
      • Must pay attention to how the antigen activates the humoral and cell-mediated branches
  • Must produce immunologic memory
      • Vaccine that produces primary response but fails to produce secondary response is not effective

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Active Immunization

  • Natural Infection with microorganism or artificial acquisition (vaccine)

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  • Both stimulate the proliferation of T and B cells, resulting in the formation of effector and memory cells

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  • The formation of memory cells is the basis for the relatively permanent effects of vaccinations

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The generation of an immune response to a vaccine

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Live, Attenuated Vaccines

  • Microorganisms can be attenuated so that they lose ability to cause significant disease
      • Retain capacity for growth in host
      • Bacteria is grown for prolonged period in adverse conditions
          • Those that survive will not be suited to grow in “better” conditions in host
      • A virus might be grown in cell type that is not normal host
          • Accumulates mutations that might weaken it
      • Measles, mumps, rubella vaccine is example

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  • For example, an attenuated strain of Mycobacterium bovis called Bacillus Calmette-Guerin (BCG) was developed by growing M. bovis on a medium containing increasing concentrations of bile.
  • The Sabin polio vaccine, consisting of three attenuated�strains of poliovirus, is administered orally to children on a sugar cube or in sugar liquid.

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Live, Attenuated Vaccines

  • Advantages
      • Can grow in host therefore producing immunologic memory with only single vaccination
      • Produces memory T cells
      • Good for distribution in Third World countries
  • Disadvantages
      • Possibility that it will revert to virulent form
        • Polio – 1 in 2.4 million chance this will happen
      • Complications
        • Measles vaccine – encephalitis
        • Out of 75 million patients between 1970 and 1993, only 48 cases
      • Danger from remaining un-vaccinated and getting disease is much greater than complications to these proven vaccines

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Inactivated or “killed” vaccines

  • Inactivation of pathogen by heat or chemical means
      • Not capable of replication in host
      • Epitopes have to be maintained after killing process
  • Often require boosters
  • Risks
      • Pathogen has to be grown in large #’s prior to inactivation – individuals involved in manufacturing are at risk
      • Some of the pathogen may not be killed
  • Pertussis vaccine, typhoid vaccine, flu vaccine, salk vaccine

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Attenuation vs. Inactivation

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Subunit Vaccines

  • Purified macromolecules derived from pathogens
  • Toxoids
      • Some bacteria are pathogenic because of exotoxins that they produce
      • Purify exotoxin, inactivate it with formaldehyde to form toxoid that can be used to immunize
  • Bacterial polysaccharide capsules
  • Viral glycoproteins are candidates
      • Little success so far

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  • The vaccine for Neisseria meningitidis, a common cause of bacterial meningitis, also consists of purified capsular polysaccharides.
  • Diphtheria and tetanus vaccines, can be made by purifying the bacterial exotoxin and then inactivating the toxin with formaldehyde to form a toxoid.

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Conjugate Vaccines

  • Polysaccharide vaccines unable to activate TH cells
      • Activate B cells in thymus-independent manner
      • IgM production but no class switching, no memory
    • Conjugate to protein carrier that is considerably more immunogenic

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ISCOMS

  • Immunostimulating Complexes

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  • Multilmeric presentation of antigen / adjuvant

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  • Enhanced cell-mediated immune response, delayed-type hypersensitivity, cytotoxic T lymphocyte response, increased Ag expression associated with MHC II

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  • (a) Solid matrix antibody-antigen complexes can be designed to contain synthetic�peptides representing both T-cell epitopes and B-cell epitopes
  • (b) Protein micelles, liposomes, and immunostimulating complexes (ISCOMs) can all be prepared with extracted antigens or antigenic peptides. In micelles and liposomes, the hydrophilic residues of the antigen molecules are oriented outward.
  • In ISCOMs, the long fatty-acid tails of the external detergent layer are adjacent to the hydrophobic residues of the centrally located antigen molecules. �

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DNA �Vaccines

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Production of vaccinia vector vaccine

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Radial immuno-diffusion is a type of precipitation reaction.

It is thus based on the principles of the precipitin curve which states that antigen-antibody interact forming visible cross-linked precipitate when the proper ratio of antigen to antibody is present.

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