Vaccines

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Vaccines

• Brandon Ore and Anitra Monroe

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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.

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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).

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• 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.

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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.

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• 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.

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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.

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• 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.

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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.

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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.

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Freunds Adjuvant

• In Freunds 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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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 vaccines
  antigens be displayed on the cells 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?

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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?

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This powerpoint presentation was taken from

• jushy.com/presentations/vaccines202.ppt