Anti-Viral Vaccines

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Anti-Viral Vaccines

• Medicinal Chemistry
• Donlene Webb
• SMU

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Viruses

• A virus is a submicroscopic obligate parasitic
  particle that infects cells in biological
  organisms.
• Viruses are non-living particles that can only
  replicate when an organism reproduces the
  virulent RNA or DNA.
• Among other things, viruses do not move,
  metabolize, or decay on their own. Viruses are
  obligate intracellular parasites that lack the
  cellular machinery for self-reproduction.
• Viruses infect eukaryotes and prokaryotes such as
  bacteria bacteriophages.
• Typically viruses carry a small amount of
  genetic material, either in the form of RNA or
  DNA, but not both, surrounded by some form of
  protective coat consisting of proteins, lipids,
  glycoproteins or a combination.
• The viral genome codes for the proteins that
  constitute this protective coat, as well as for
  those proteins required for viral reproduction
  that are not provided by the host cell.

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Viruses

• Viral nucleic acid can be DNA or RNA. It can be
  single or double stranded, circular or linear,
  with most being linear.
• The nucleic acid is protected from physical,
  chemical and enzymatic damage by a protein coat
  called a Capsid.
• Many viruses have a second envelope surrounding
  the Capsid on which there are spikes with
  antigenic determinants.
• This outer surface of the virus is responsible
  for host cell recognition. Initially viral
  proteins on the outer surface will attach to the
  hosts receptor molecules. A simplified viron is
  illustrated below.

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Life Cycle

• ? Attachment, sometimes called absorption The
  virus attaches to receptors on the host cell
  wall.
• Injection The nucleic acid of the virus moves
  through the plasma membrane and into the
  cytoplasm of the host cell. The capsid of a
  phage, a bacterial virus, remains on the outside.
  In contrast, many viruses that infect animal
  cells enter the host cell intact.
• Transcription Within minutes of phage entry into
  a host cell, a portion is transcribed into mRNA,
  which is then translated into proteins specific
  for the infecting phage.
• Replication The viral genome contains all the
  information necessary to produce new viruses.
  Once inside the host cell, the virus induces the
  host cell to synthesize the necessary components
  for its replication.
• Assembly The newly synthesized viral components
  are assembled into new viruses.
• Release Assembled viruses are released from the
  cell and can now infect other cells, and the
  process begins again.

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Origin of Vaccines

• Smallpox was the first disease people tried to
  prevent by purposely inoculating themselves with
  other types of infections. Inoculation is
  believed to have started in India or China before
  200 BC. Physicians in China immunized patients by
  picking off pieces from drying pustules of a
  person suffering from a mild case of smallpox,
  grinding the scales to a powdery substance, and
  then inserting the powder into the person's nose
  in order for them to be immunized. In 1718, Lady
  Mary Wortley Montague reported that the Turks
  have a habit of deliberately inoculating
  themselves with fluid taken from mild cases of
  smallpox. Lady Montague inoculated her own
  children in this manner. In 1796, during the
  heyday of the smallpox virus in Europe, an
  English country doctor, Edward Jenner, observed
  that milkmaids would sometimes become infected
  with cowpox through their interactions with dairy
  cows' udders. Cowpox is a mild relative of the
  deadly smallpox virus. Building on the
  foundational practice of inoculation, Jenner took
  infectious fluid from the hand of milkmaid Sarah
  Nelmes. He inserted this fluid, by scratching or
  injection, into the arm of a healthy local eight
  year old boy, James Phipps. Phipps then showed
  symptoms of cowpox infection. Forty-eight days
  later, after Phipps had fully recovered from
  cowpox, Jenner injected some smallpox-infected
  matter into Phipps, but Phipps did not later show
  signs of smallpox infection

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Timeline of Vaccines

• 18th century
• 1796 First vaccine for smallpox, first vaccine
  for any disease
• 19th century
• 1882 First vaccine for rabies
• 20th century
• 1932 First vaccine for yellow fever
• 1945 First vaccine for influenza
• 1952 First vaccine for polio
• 1954 First vaccine for Japanese encephalitis
• 1957 First vaccine for adenovirus-4 and 7
• 1962 First oral polio vaccine
• 1964 First vaccine for measles
• 1967 First vaccine for mumps
• 1970 First vaccine for rubella
• 1974 First vaccine for chicken pox
• 1977 First vaccine for pneumonia
• 1978 First vaccine for meningitis
• 1981 First vaccine for hepatitis B
• 1992 First vaccine for hepatitis A

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Vaccines

• The principle of vaccination is to induce a
  "primed" state in the vaccinated subject so that,
  following exposure to a pathogen, a rapid
  secondary immune response is generated leading to
  the accelerated elimination of the organism and
  protection from clinical disease. Success depends
  on the generation of memory T and B cells and the
  presence in the serum of neutralizing antibody.
• Attributes of a good vaccine
• 1.Ability to elicit the appropriate immune
  response for the particular pathogen
• Tuberculosis - cell mediated response
• most bacterial and viral infections - antibody
• 2. Long term protection    ideally life-long3.
  Safety    vaccine itself should not cause
  disease4. Stable    retain immunogenicity,
  despite adverse storage conditions prior to
  administration5. Inexpensive

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Live Vaccines

• 1. Live attenuated organisms
• Organisms whose virulence has been artificially
  reduced by in vitro culture under adverse
  conditions, such as reduced temperature. This
  results in the selection of mutants which
  replicate poorly in the human host and are
  therefore of reduced virulence.  Replication of
  the vaccine strain in the host reproduces many of
  the features of wild type infection, without
  causing clinical disease.  Most successful viral
  vaccines belong to this group.
• The immune response is usually good - when the
  virus replicates in the host cells, both antibody
  as well as cell mediated immune responses are
  generated and immunity is generally long lived.
   Often, only a single dose is needed to induce
  long term immunity.

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Schematic Diagram of Development of Attenuated
Cell Strain
2. Heterologous vaccines Closely related
organism of lesser virulence, which shares many
antigens with the virulent organism. The vaccine
strain replicates in the host and induces an
immune response that cross reacts with antigens
of the virulent organism. The most famous example
of this type of vaccine is vaccinia virus   Both
cowpox virus and vaccinia virus are closely
related to variola virus, the causitive agent of
smallpox. Widespread use of vaccinia virus as a
vaccine has lead to the world-wide eradication of
smallpox.
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Live Vaccines

• 3. Live recombinant vaccines
• It is possible, using genetic engineering, to
  introduce a gene coding for an immunogenic
  protein from one organism into the genome of
  another (such as vaccinia virus). The organism
  expressing a foreign gene is called a
  recombinant. Following injection into the
  subject, the recombinant organism will replicate
  and express sufficient amounts of the foreign
  protein to induce a specific immune response to
  the protein.
• Attributes
• Good immune response
• Both Cell Mediated Immunity and antibody
  responses.
• Immunity is long lived
• Single dose
• Safety
• Danger of reversion to virulence, or
• Severe disease in immunocomprised
• Stability
• Organisms in the vaccine must remain viable in
  order to infect and replicate in the host
• Vaccine preparations are therefore very sensitive
  to adverse storage conditions
• Maintenance of the cold chain is very important.
• Expense
• Cheap to prepare

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Vaccinia Virus

• The most unusual, and perhaps
  technologically the most useful, feature of
  poxviruses is their ability to replicate in the
  infected cell's cytoplasm, and not nucleus.
  Infectious virions have a lipoprotein envelope
  surrounding a complex core of linear duplex DNA
  connected at each end by hairpin loops. Virus
  encoded enzymes, a multi-subunit DNA-dependent
  RNA polymerase, a transcription factor, capping
  and methylating enzymes, and a poly(A) polymerase
  are all contained within the core. Vaccinia is
  therefore well equipped to synthesize
  translatable mRNA.

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Vaccinia Virus

• Vaccinia undergoes homologous recombination
  during replication in infected cells. When used
  as an expression vector, this innate ability to
  recombine is used to introduce foreign DNA
  coupled to a vaccinia promoter. The steps below
  outline the construction of the vaccinia
  expression vector.
• (1) The gene (YFG) is flanked with vaccinia DNA
  sequences, especially the vaccinia promoters and
  multicloning sites for cleavage and ligation.
• The following are often included
• The promoters are necessary DNA sequences because
  the endogenous viral RNA polymerase binds here to
  initiate transcription. The promoter also
  determines the direction of translation for the
  insert, and more importantly the ability to
  express proteins (depending on how tightly
  regulated the promoter is).
• In addition, DNA sequences, such as the
  lacO/lacIq repressor system, that act in
  conjunction with promoters and also bind
  repressor molecules can regulate the induction of
  transcription. Hence, by adding or removing a
  particular substrate, expression of YFG can be
  turned on and off as necessary.
• Stabilizing elements such as transcription
  terminators can also be incorporated downstream
  of the multicloning site. These anti-termination
  elements signal the RNA polymerase to release the
  DNA template and stop transcription, and prevent
  pausing, pre-mature termination, and overreading
  which adversely affect plasmid replication.
• Finally, small open reading frames, known as
  ribosome binding sites, upstream of YFG, can be
  included to encourage binding and translation of
  the target sequence.

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Vaccinia Virus

• (2) The product (usually a plasmid with an ori
  and a marker gene) is then inserted into a cell
  infected with the whole virus. The whole virus
  must be used because it contains the necessary
  enzymes and factors within its core.
• (3) Recombination during replication leads to
  insertion of YFG (i.e. the foreign DNA) into the
  viral progeny. The usual target of insertion is a
  nonessential region, so that virus retains its
  ability to replicate independently and the system
  can be maintained. The estimated incidence of
  successful insertion is approximately 0.1 (hey,
  I didn't say this was easy...). A major advantage
  of the vaccinia vector is that atleast 25,000 bp
  of DNA (a lot more than most vectors can handle)
  can be added to the vaccinia genome without
  requiring any deletions.
• (4) Controlling when and how much of YFG is
  expressed is easy because the poxvirus promoter
  sequences control the rate and time of
  expression, and you can regulate which promoters
  are in the system. The highest yeilds of protein
  are generally generated with the late promoters.
• (5) Virus plaques can finally be screened by DNA
  hybridization or for expression of your favorite
  protein.
• With the rapid discovery of new genes, especially
  from the Human Genome Project, comes the daunting
  task of understanding how the products of these
  genes are synthesized, regulated, and used within
  cells. Vaccinia virus, as a vector for expression
  systems, is a powerful addition to the range of
  molecular methods available for such purposes.
  The use of Vaccinia allows temporal, as well as
  quantitative regulation of protein expression.
  More importantly, Vaccinia is large enough to
  accomodate several gene inserts while preserving
  the entire length of its DNA. Finally, as an
  infectious agent, it can target specific cells
  for insertion, and may thus be employed in gene
  and cancer therapy. Led by Vaccinia, the
  Poxviridae may no longer be considered the
  scourge of the world, but rather powerful tools
  for advancing research and therapeutic avenues.

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Killed (inactivated) vaccines

• When safe live vaccines are not available, either
  because attenuated strains have not been
  developed or else because reversion to wild type
  occurs too readily, it may be possible to use an
  inactivated  preparation of the virulent organism
  to immunize the host.
• The organism is propagated in bulk, in vitro, and
  inactivated with either beta-propiolactone or
  formaldehyde. These vaccines are not infectious
  and are therefore relatively safe. However, they
  are usually of lower immunogenicity and multiple
  doses may be needed to induce immunity. In
  addition, they are usually expensive to prepare.
• Subcellular fractions
• When protective immunity is known to be directed
  against only one or two proteins of an organism,
  it may be possible to use a purified preparation
  of these proteins as a vaccine. The organism is
  grown in bulk and inactivated, and then the
  protein of interest is purified and concentrated
  from the culture suspension. These vaccines are
  safe and fewer local reactions occur at the
  injection site. However, the same disadvantages
  of poor immunogenicity and the need for multiple
  boosters applies.
• Recombinant proteins
• Immunogenic proteins of virulent organisms may be
  synthesized artificially by introducing the gene
  coding for the protein into an expression vector,
  such as E-coli or yeasts. The protein of interest
  can be extracted from lysates of the expression
  vector, then concentrated and purified for use as
  a vaccine. The only example of such a vaccine, in
  current use, is the hepatitis B vaccine.

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Killed (inactivated) vaccines

• Attributes
• Immune response
• poor  only antibody - no cell immediated immune
  response.
• response is short-lived and multiple doses are
  needed.
• may be enhanced by the incorporation of adjuvants
  into the vaccine preparation (see below)
• 1. Safety
• Inactivated, therefore cannot replicate in the
  host and cause disease.
• Local reactions at the site of injection may
  occur.
• 2. Stability
• Efficacy of the vaccine does not rely on the
  viability of the organisms.
• These vaccines tend to be able to withstand more
  adverse storage conditions.
• 3. Expense
• Expensive to prepare

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Adjuvants

• Certain substances, when administered
  simultaneously with a specific antigen, will
  enhance the immune response to that antigen. Such
  compounds are routinely included in inactivated
  or purified antigen vaccines.
• Adjuvants in common use
• Aluminium salts
• First safe and effective compound to be used in
  human vaccines.
• It promotes a good antibody response, but poor
  cell mediated immunity.
• Form precipitate with antigen, making complex
  more antigenic
• 2. Liposomes and Immunostimulating complexes
  (ISCOMS)
• 3. Complete Freunds adjuvant is an emulsion of
  Mycobacteria, oil and water
• Too toxic for man
• Induces a good cell mediated  immune response.
• 4. Incomplete Freund's adjuvant as above, but
  without Mycobacteria.
• 5. Muramyl di-peptide
• Derived from Mycobacterial cell wall.
• 6. Cytokines
• IL-2, IL-12 and Interferon-gamma.
• Possible modes of action
• By trapping antigen in the tissues,  thus
  allowing maximal exposure to dendritic cells and
  specific T and B lymphocytes.
• By activating antigen-presenting cells to secrete
  cytokines that enhance the recruitment of
  antigen-specific T and B cells to the site of
  inoculation.

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Subunit Vaccines

• Immune response can be stimulated by one or a set
  of viral proteins.
• This was first demonstrated by hepatitis B and
  influenza vaccines
• These can be a lot safer than attenuated or
  inactivated vaccines
• The subunits included are determined by
  identifying which proteins the antibodies
  recognize.
• Subunits vaccines
• Composed solely of purified protein
• can be delivered to body by means of a
  nonpathogenic virus, bacteria, etc

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DNA Vaccines

• DNA vaccines are at present experimental, but
  hold promise for future therapy since they will
  evoke both humoral and cell-mediated immunity,
  without the dangers associated with live virus
  vaccines.
• The gene for an antigenic determinant of a
  pathogenic organism is inserted into a plasmid.
   This genetically engineered plasmid comprises
  the DNA vaccine which is then injected into the
  host.  Within the host cells, the foreign gene
  can be expressed (transcribed and translated)
  from the plasmid DNA, and if sufficient amounts
  of the foreign protein are produced, they will
  elicit an immune response.
• in recent years a new type of vaccine, created
  from an infectious agent's DNA called DNA
  vaccination, has been developed. It works by
  insertion (and expression, triggering immune
  system recognition) into human or animal cells,
  of viral or bacterial DNA. These cells then
  develop immunity against an infectious agent,
  without the effects other parts of a weakened
  agent's DNA might have. As of 2006, DNA
  vaccination is still experimental, but shows some
  promising results.

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Vaccines in General Use

• Measles
• Live attenuated virus grown in chick embryo
  fibroblasts, first introduced in the 1960's. Its
  extensive use has led to the virtual eradication
  of measles in the first world. In developed
  countries, the vaccine is administered to all
  children in the second year of life (at about 15
  months). However, in developing countries, where
  measles is still widespread, children tend to
  become infected early (in the first year), which
  frequently results in severe disease. It is
  therefore important to administer the vaccine as
  early as possible (between six months and a
  year). If the vaccine is administered too early,
  however, there is a poor take rate due to the
  interference by maternal antibody. For this
  reason, when vaccine is administered before the
  age of one year, a booster dose is recommended at
  15 months.

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MeaslesUnited States, 1950-2002

• Vaccine Licensed

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Vaccines in General Use

• Mumps
• Live attenuated virus developed in the 1960's.  
  In first world countries it is administered
  together with measles and rubella at 15 months in
  the MMR vaccine.
• The current "Jeryl Lynn" strain of the mumps
  vaccine was developed by Dr. Maurice Hillman from
  the mumps virus that infected his 5-year-old
  daughter (whose name was Jeryl Lynn). This
  vaccine, combined with rubella or both rubella
  and measles vaccines (MMR), has been widely used
  worldwide (300 million doses given) since it was
  approved by the FDA in 1967.

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• MumpsUnited States, 1968- 2002

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Vaccines in General Use

• Polio
• Two highly effective vaccines containing all 3
  strains of poliovirus are in general use
• The killed virus vaccine (Salk, 1954) is used
  mainly in Sweden, Finland, Holland and Iceland.
• The live attenuated oral polio vaccine (Sabin,
  1957) has been adopted in most parts of the
  world  its chief advantages being low cost, the
  fact that it induces mucosal immunity and the
  possibility that, in poorly immunized
  communities, vaccine strains might replace
  circulating wild strains and improve herd
  immunity.  Against this is the risk of reversion
  to virulence (especially of types 2 and 3) and
  the fact that the vaccine is sensitive to storage
  under adverse conditions. - Orimune
• The inactivated Salk vaccine is recommended for
  children who are immunosuppressed.
• 3 types of live polio virus, magnesium chloride,
  amino acid, polysorbate 80, purified water,
  neomycin, sulphate, streptomycin, penicillin and
  monkey kidney cell cultures.

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• PoliomyelitisUnited States, 1950-2002

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Vaccines in General Use

• Rubella
• Live attenuated virus. Rubella causes a mild
  febrile illness in children, but if infection
  occurs during pregnancy, the fetus may develop
  severe congenital abnormalities. Two vaccination
  policies have been adopted in the first world. In
  the USA, the vaccine is administered to all
  children in their second year of life (in an
  attempt to eradicate infection), while in
  Britain, until recently, only post pubertal girls
  were vaccinated.  It was feared that if the
  prevalence of rubella in the community fell, then
  infection in the unimmunized might occur later -
  thus increasing the likelihood of infection
  occurring in the child-bearing years.  This
  programme has since been abandoned in Britain and
  immunization of all children is the current
  practice.
• MMR live measles virus, live mumps virus, live
  rubella virus, chick embryo, human foetal cells,
  neomycin, sorbitol, gelatine.

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• RubellaUnited States, 1966-2002

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Vaccines in General Use

• Rabies
• No safe attenuated strain of rabies virus has yet
  been developed for humans. Vaccines in current
  use include
• The neurotissue vaccine - here the virus is grown
  in the spinal cords of rabbits, and then
  inactivated with beta-propiolactone. There is a
  high incidence of neurological complications
  following administration of this vaccine due to a
  hypersensitivity reaction to the myelin in the
  preparation and largely it has been replaced by
• A human diploid cell culture-derived vaccine
  (also inactivated) which is much safer.
• There are two situations where vaccine is given
  a) Post-exposure prophylaxis, following the bite
  of a rabid animalA course of 5-6 intramuscular
  injections, starting on the day of exposure.
  Hyperimmune rabies globulin may also administered
  on the day of exposure.
• b) Pre-exposure prophylaxis is used for
  protection of those whose occupation puts them at
  risk of infection with rabies  for example,
  vets, abbatoir and laboratory workers. This
  schedule is 2 doses one month apart ,and a
  booster dose one year later. (Further boosters
  every 2-3 years should be given if risk of
  exposure continues).

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Rabies
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Vaccines in General Use

• Hepatitis B
• Two vaccines are in current use a serum derived
  vaccine and a recombinant vaccine. Both contain
  purified preparations of the hepatitis B surface
  protein.
• The serum derived vaccine is prepared from
  hepatitis B surface protein, purified from the
  serum of hepatitis B carriers. This protein is
  synthesised in vast excess by infected
  hepatocytes and secreted into the blood of
  infected individuals. A vaccine trial performed
  on homosexual men in the USA has shown that,
  following three intra-muscular doses at 0, 1 and
  6 months, the vaccine is at least 95 protective.
  
• A second vaccine, produced by recombinant DNA
  technology, has since become available.
  Previously, vaccine administration was restricted
  to individuals who were at high risk of exposure
  to hepatitis B, namely infants of hepatitis B
  carrier mothers, health care workers, homosexual
  men and intravenous drug abusers. However,
  hepatitis B has been targetted for eradication ,
  and since 1995 the vaccine has been included in
  the universal childhood immunization schedule.
  Three doses are given  at 6, 10, and 14 weeks of
  age. As with any killed viral vaccines, a booster
  will be required at some interval (not yet
  determined, but about 5 years) to provide
  protection in later life from hepatitis B
  infection as a venereal disease.
• HEPATITIS B Hepatitis B virus gene, aluminium
  hydroxide, mercury, formaldehyde. For the
  genetically engineered vaccine aluminium
  hydrochloride, sodium chloride and mercury.
• Hepatitis A
• A vaccine for hepatitis A has been developed from
  formalin-inactivated , cell culture-derived
  virus. Two doses, administered one month apart,
  appear to induce high levels of neutralising
  antibodies.  The vaccine is recommended for
  travellers to third world countries, and indeed
  all adults who are not immune to hepatitis A.

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Vaccines in General Use

• Influenza
• Repeated infections with influenza virus are
  common due to rapid antigenic variation of the
  viral envelope glycoproteins. Antibodies to the
  viral neuraminidase and haemagglutinin proteins
  protect the host from infection.   However,
  because of the rapid  antigenic variation, new
  vaccines, containing antigens derived from
  influenza strains currently circulating in the
  community, are produced every year.  
  Surveillance of influenza strains now allows the
  inclusion of appropriate antigens for each
  season.The vaccines consist of partially purified
  envelope proteins of inactivated current
  influenza A and B strains.
• Individuals who are at risk of developing severe,
  life threatening disease if infected with
  influenza should receive vaccine.   People at
  risk include the elderly, immunocompromised
  individuals, and patients with cardiac disease.
  In these patients, protection from disease is
  only partial, but the severity of infection is
  reduced.
• Varicella-Zoster virus
• A live attenuated strain of varicella zoster
  virus has been developed.  It is not licensed in
  South Africa for general use, but is used in some
  oncology units to protect immuno-compromised
  children who have not been exposed to wild-type
  varicella zoster virus. Such patients may develop
  severe, life threatening infections if infected
  with the wild type virus.

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Vaccines in General Use

• Yellow Fever
• The 17D strain is a live attenuated vaccine
  developed in 1937. It is a highly effective
  vaccine which is administered to residents in the
  tropics and travellers to endemic areas. A single
  dose induces protective immunity to travellers
  and booster doses, every 10 years, are
  recommended for residents in endemic areas.

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Virus Vaccine Brand Name Type Route
Hepatitis A Havrix Inactivated Intramuscular
Hepatitis A VAQTA Inactivated Intramuscular
Hepatitis B Recombivax Subunit Intramuscular
Hepatitis B Engerix-B Subunit Intramuscular
Influenza Fluzone Whole Inactivated Intramuscular
Influenza Fluzone, FlueShield Split-Virion Intramuscular
Influenza Fluvirin Subunit Intramuscular
Japanese Encephalitis JE-Vax Inactivated Subcutaneous
Measles Attenuvax Live Attenuated Subcutaneous
Mumps Mumpsvax Live Attenuated Subcutaneous
Polio Orimune Inactivated Salk Subcutaneous
Polio IPOL, Poliovax Live Attenuated Sabin Oral
Rabies HDCV Inactivated Intramuscular
Rabies RVA Inactivated Intramuscular
Rabies RabAvert Inactivated Intramuscular
Rotavirus RotaShield Live Attenuated Oral
Rubella Meruvax II Live Attenuated Subcutaneous
Varicella-Zoster Varivax Live Attenuated Intramuscular
Yellow Fever YF-Vax Live Attenuated Subcutaneous
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Vaccine Controversy

• The public health benefits of vaccinations are
  exaggerated. Critics of vaccination policy point
  out that the mortality rates of some illnesses
  were already dramatically reduced before vaccines
  were introduced, and claim that further
  reductions cannot immediately be attributed to
  vaccines.
• Secondary and long-term effects on the immune
  system from introducing immunogens directly into
  the bloodstream are not fully understood.
• The recommended vaccination schedule does not
  consider the cumulative effect of being exposed
  to multiple immunogens at the same time and at a
  young age.
• At least some vaccine studies did not include
  such young children (e.g., 5 week old infants, 2
  month old infants), yet vaccination schedules
  start with newborns. There can be a vast
  difference between the weight and all around
  development of a newborn baby versus a toddler,
  yet this is not accounted for.
• claims diseases including leukemia, MS, sids,
  autism, and others were rare, and have increased
  coinciding with the increased use of
  vaccinations, and that this is due to
  vaccinations.
• Opponents of current vaccination policy question
  if vaccinations actually create immunity against
  the targeted diseases because some people who
  have been vaccinated still contracted the
  illness.

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Vaccine Controversy

• By not exposing children to common childhood
  illnesses, they may be more susceptible to
  diseases at a point when their immune system is
  weakened.
• Vaccinations contain chemical components that are
  known to be toxic, such as formaldehyde, aluminum
  in various compounds, acetone, glyceride,
  ethylene glycol, and neomycin when injected in
  large enough quantities.
• As is true with any medication, adverse events to
  the vaccine (even when rare) may be worse than
  the disease itself.
• There are a number of possible conflicts of
  interest that may affect the research design,
  findings, and opinions about vaccines, including
  financial interests of companies, the
  self-regulatory mechanism of medical doctors, and
  fear of the consequences should vaccines be found
  to be dangerous..
• Some researchers hypothesize possible links
  between the increasing incidence of cancer and
  use of vaccines, suggesting links to the way
  vaccines may alter the cells in our bodies.

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Latest Discoveries and News

• CHINA - The Chinese government has given the
  go-ahead to a Shanghai-based pharmaceutical firm
  to begin clinical trials of Tamiflu, an
  anti-viral drug that is believed to be the best
  defense against bird flu in humans. The drug
  will be manufactured by Shanghai Sunve
  Pharmaceutical Co Ltd under a licensing
  arrangement with Swiss drug producer Roche. The
  study will try to find out if the Tamiflu
  produced by the Shanghai firm is as effective as
  that produced by Roche.
• Smallpox

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References

• AAPPublications.org - 'Thimerosal and the
  Occurrence of Autism Negative Ecological
  Evidence From Danish Population-Based Data'
  Pediatrics, Vol 112, No 3, September 2003
  (Denmark study on autism rates)
• BMJJournals.com - 'Comparative efficacy of three
  mumps vaccines', Matthias Schlegel, Joseph J.
  Osterwalder, Renato L. Galeazzi, Pietro J.
  Vernazza, British Medical Journal' Vol 319, No
  352, August 7, 1999
• BrianDeer.com - 'Ileal-lymphoid-nodular
  hyperplasia, non-specific colitis, and pervasive
  developmental disorder in children' Andrew
  Wakefield, et al., The Lancet, Vol 351, No 9103,
  February 28, 1998
• Read Congressional Research Service (CRS) Reports
  regarding vaccines
• JPandS.org (pdf) - 'Thimerosal in Childhood
  Vaccines, Neurodevelopment Disorders, and Heart
  Disease in the United States', Mark Geier, M.D.,
  Ph.D., and David Geier, B.A., Journal of American
  Physicians and Surgeons, Vol 8, No 1, Spring,
  2003
• Vaccine Information.org - 'Vaccine Information
  for the Public and Health Professionals'
• 11 Vaccine history from smithsonian institute
• http//www.coldcure.com/html/smallpox.html
  article on timeline of vaccine history

45
References

• http//www.sh.lsuhsc.edu/IntraGrad/micro/OLD-Micro
  289/2003/28920PID200320Vaccines20.DOC
• http//www.bio.davidson.edu/Courses/Molbio/MolStud
  ents/01teparakh/Methods.htm
• http//web.uct.ac.za/depts/mmi/jmoodie/vacc2.html