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					     Vaccines



   Seminar by M. Arun kumar
           What is a Vaccine?
   A vaccine is a non-pathogenic antigen that
    mimics a particular pathogen in order to
    elicit an immune response as if that actual
    pathogen were in the body.

   The overall goal of a vaccine is to establish
    immunity against that particular pathogen.
    The Mechanism of a Vaccine
   In an ideal scenario, whenever
    a vaccine is first administered,
    it is phagocytized by an
    antigen presenting cell (APC).
   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 (Th cells).
   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.
   Memory T-cells are also
    established, however, they
    usually have a shorter half-life
    than memory B cells, thus,
    they play only a minor role in
    long-term immunity.
   Usually, there are no cytotoxic
    T-cells formed whenever the
    body responds to a vaccine.
    Potential Shortcomings of Vaccines
    In some rare cases, a vaccine may
     directly activate a B cell, without
     stimulation from Th cells.
    Such antigens are known as T-
     independent (TI) antigens.
    The problem with such a response
     is that only Ig-M antibodies are
     produced and there are no
     memory cells established.
    Thus, such a vaccine will be
     useless against establishing
     immunity.
   Sometimes, the vaccine may be cleared from the body before it has
    the chance to properly stimulate the immune system.

   Some pathogens, particularly viruses, has a tendency to mutate and
    change there surface antigens, making a vaccine against them
    ineffective.

        This is especially true of malaria, which is constantly changing its
         surface antigens.

   Several different types of pathogens may cause similar infections,
    thus, several different vaccines may be required for them.

        For example, Heamophilus influenzae, a bacterium, and influenzavirus,
         a virus, causes diseases with similar symptoms.
    The Importance of the 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.
   But in some cases, a pathogen may be so virulent that it
    causes illness, even during the secondary immune response.
   In this situation, a vaccine may be ineffective.
               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.
    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.
                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.
    Immune Stimulatory Complexes
    Consists of open cage-like
     structures that contains
     cholesterol and a mixture of
     saponins.
    Allows delivery of the vaccine
     to the cytosol, which
     stimulates a response by
     cytotoxic T-cells .
    Such an adjuvant may be
     particularly useful in a vaccine
     against cancer.
         Routes of Administration
   There are three different routs
    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.
                           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.
   Boosters can also be given
    during the primary response in
    order to prolong and
    strengthen the immune
    response against the vaccine.
           Types of Vaccines
   There are numerous types of vaccines.
   Each different type of has its own unique
    properties.
   There function, however, is the same, to
    establish immunity against a particular
    pathogen.
      Attenuated Virus/Bacteria
   These vaccines consist of live, but
    weakened, viruses or bacteria.
   These organisms have been altered, either
    genetically or chemically, in a way that
    they are not pathogenic.
   An example is the attenuated virus vaccine
    for yellow fever, which utilizes the YF17D
    strain, a weakened form of the wild virus.
         Killed Whole Organism
   This vaccine consist of
    the actual pathogen,
    however, it has been
    killed, either by a heat
    treatment or chemically.
   An example is the Salk
    vaccine for polio, which
    utilizes whole
    polioviruses that have
    been inactivated by
    formaldehyde.
                              Toxoids
   Some species of bacterial
    produce what is known as
    exotoxens.
   Toxoids are vaccines which
    consist of exotoxins that have
    been inactivated, either by heat
    or chemicals.
   These vaccines are intended to
    build an immunity against the
    toxins, but not necessarily the
    bacteria that produce the
    toxins.
   Some examples are botulinum
    antitoxen and diphtheria
    antitoxen.
             Surface Molecules
   Proteins, carbohydrates, and lipids, that are found
    on the surface of pathogens, are isolated and used
    as a vaccine.
   Proteins are usually large and complex enough to
    be used on there own.
   Carbohydrates and lipids requires conjugated
    with a large protein in order to be immunogenic.
   An example of surface molecules used as a
    vaccine are hepatitis B surface antigens.
            Anti-Idiotype Vaccines
   In this unique type of vaccine,
    antibodies from a sick individual are
    isolated.
   These antibodies are then injected into
    a lab animal, which may then produce
    an antibody whose antigen binding
    site mimics the epitope that the
    original antibody binds to.
   These antibodies are then isolated and
    injected into a healthy individual, who
    may produce antibodies with an
    antigen binding site that binds to the
    antigen binding site of the animals
    antibodies.
   Because the animals binding site
    resembles the epitope of an antigen on
    a particular pathogen, the individual
    will have an immunity against that
    pathogen.
                   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.
             Chimeric Vaccines
   Chimeric vaccines usually consist of attenuated viruses
    that have been engineered to carry antigens from multiple
    types of pathogens.
   For example, the yellow fever vaccine YF17D has been
    engineered to carry antigens from HIV, different types of
    bacteria, malaria, even cancer.
   The main of a chimeric vaccine is the establishment of
    immunity against several different diseases with one
    administration.
    Vaccine Production Methods
   There are three main vaccine 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.
                               In-Vivo
   In in-vivo manufacturing, the
    vaccine is produced inside a living
    organism.
   Embryonated Chicken eggs are
    are commonly used, particularly
    in producing flu vaccines.
   Vaccines, such as 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.
                          In-Vitro
   Here, using recombinant DNA
    technology, vaccines can be
    produced in yeast cultures,
    bacterial cultures, or cell
    cultures.
   Recombinant vaccines, such as
    chimeric vaccines, are
    produced in this manor.
   Attenuated virus/bacteria
    vaccines can also be produced
    this way.
               Chemical Synthesis
   Here, instead of using
    biological systems to
    produce a vaccine, a vaccine
    can be produced in a lab.
   Vaccines that utilize
    synthetic peptides as well as
    conjugated lipids and
    polysaccharides are
    manufactured this way.
   Usually, this method is used
    in combination with either
    in-vivo or in-vitro
    production.
    Risks Associated With Vaccines
    The primary risk associated with vaccines, especially vaccines that
     utilize live organisms, is that the vaccine itself causes illness.
          This Happened with the orally administered Sabin vaccine for
           polio, where some individuals became ill and, in rare cases,
           even spread the illness to other individuals who were not
           exposed to the vaccine.
    Another risk is that the vaccine may behave as a super antigen and
     over stimulate the immune system.
    Yet a third risk is that some individuals may have an allergic reaction
     to the vaccine, especially vaccines produced in embrionated chicken
     eggs and in transgenic plants.
Specific Antigens: Viruses and Bacteria
   Almost every type of
    viral and bacterial
    pathogen has a vaccine,
    or, there is one under
    development for it.
   This is because Vaccines
    use viral or bacterial
    components which causes
    the immune system to
    react as if an actual virus
    or bacterium has invaded
    the body.
                          Parasites
   Currently the only vaccines
    being developed for
    parasites are vaccines for
    protozoa, particularly the
    protozoan Plasmodium, the
    causative agent of malaria.
   Because of its complex life-
    cycle and its tendency to
    regularly change its surface
    antigens, the development of
    a malaria vaccine has been
    difficult to achieve.
                                  Cancer
   Any type of vaccine against
    cancer must be able to elicit a
    response by cytotoxic T-cells,
    which is something conventional
    vaccines do not do.
   In order for a vaccine to do this, it
    has to be taken up by the cancer
    cell and the vaccine’s antigens be
    displayed on the cell’s MHC-I
    molecules.
   In this case, the cancer must be
    present before the vaccine can be
    administered.
   So, does this really make it a
    vaccine?
                                Nicotine
   Perhaps the most unusual “pathogen”
    that a vaccine is being developed for
    is nicotine
   A vaccine consisting of nicotine,
    which is a hapten, conjugated to a
    larger carrier molecule.
   When administered, the body will
    actually mount an immune response
    and produce antibodies against
    nicotine.
   The problem with this vaccine is that
    nicotine by itself will not cause an
    immune response, even if memory
    cells against it exist.
   Thus, the “vaccine” must be
    administered, in large doses, along
    with administration of nicotine.
   So, is this really a vaccine?
 Thank   u

				
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