Vaccines and Immunizations

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Vaccines and Immunizations

• Sidelsky
• 2007

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Immunization

• The induction of artifical immunity
• by giving preformed antibodies
• ( immunoglobulins)
• Administration of an antigen ( active
• Immunization)

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Immunity and immunoglobulins

• Non Specific - collected from pooled serum of a
  high titer
• Effective for short duration( 1-4 months)
• Broken down in protein catabolism and recycled

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Vaccines

• Vaccines contain an antigen to which the immune
  system responds
• Vaccines contain weakened or attenuated viruses
  or organisms, inactivated organisms
• Portions of organisms
• Toxoids which are inactivated toxins that are
  antigenic, but not harmful

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Mechanism of response

• Upon administration of the vaccine
• The immune system reacts to it as
• foreign
• The response is a weaker version of the one that
  would occur in the face of the actual pathogen
• The response of the immune system determines the
  efficacy of the immunzation and the extent of the
  immunity provided

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Boosters

• Required to sustain immunity
• The first dose evokes a primary immune response
• The subsequent doses help to stimulate a
  secondary immune response
• This increases the length of time that antibodies
  are present to prevent disease
• May also affect the strength of response to the
  organism if the individual is exposed

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Type of vaccine

• The route of administration of a disease can
  affect the quality of immunity
• Comparable to the injection of vaccines into
  muscle, the response is more effective if the
  vaccine is administered through its normal route
  of entry

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DTaP

• Diptheria, Tetanus, and acellular Pertussis
• Replaced old DTP
• Safer to administer
• Made by pruifying toxins as well as proteins
• These are inactivated by formaldehyde

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Protection and side effects

• The DTaP protects vaccine protects against,
  Diptheria, Tetanus, and Pertussis
• Pertussis is the most problematic aspect of the
  disease
• Protects agains whooping cough
• Hooping cough is an upper respiratory infection
  that is caused by Bordatella pertussis

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Whooping Cough ( continued)

• The old vaccine caused fever, redness, at the
  injection site, malaise.
• Crying persistently was also a side effect
• Seizures were observed in some
• In Japan they stopped administration of the
  vaccine.
• A the time they stopped there wer 400 cases a
  year, this increased to 13.000 with much higher
  mortality

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Diptheria

• Diptheria is caused by an organism called
  Cornybacterium diptheriae
• The disease itself is caused by a toxin
• The toxin causes the formation of a membrane
  across the back of the throat making it difficult
  to breath

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Diptheria

• Early stages Sore throat. Low fever.
• Swollen neck glands.
• Late stages Airway obstruction and breathing
  difficulty. Shock (low blood pressure, rapid
  heartbeat, paleness, cold skin, sweating, and
  anxious appearance) (Kadirova, R. et al. Journal
  of Infectious Diseases, 2000181S110-S115
  Hadfield, T. L. et al. Journal of Infectious
  Diseases, 2000181S116-S120.

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Diptheria
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Tetanus

• Caused by the bacteria, Clostridium tetani
• Natural soil baterium
• Enters the body through a wound
• The bacterium produces a toxin that affects the
  skeletal muscle
• Vaccine provides immunity
• Td
• Requires booster every 10 years

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Tetanus
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Polio

• Caused by an enterovirus
• Enters the body through the oral route
• Enters through the gastrointestinal route

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Polio

• Causes fever, diarrhea,vomiting, and still neck
  in some children
• More severe form paralysis
• Usually legs and arms are paralyzed - some times
  chest muscles that involve breathing.

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Global Incidence of Polio - 1995
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Polio Pioneers
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Philadephia Connection Dr. Hilary Koprowski
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Polio vaccines

• OPV - oral vaccine - changes the genetics of the
  virus
• The virus can survive in the GI tract, but cannot
  enter the nervous system
• Antibodies are made on the surface of the gastric
  mucosa as well as the blood

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IPV

• IPV made by inactivating the virus with
  formaldehyde
• Administered as an IM shot
• Provides more immunity in blood but does not
  protect the gastrointestinal route
• IPV provides a second line of defense against the
  organism

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Vaccine administration and recommendations

• Two doses of IVP followed by two doses of OVP(
  new vaccine eIVP) enhanced potency inactivated
  polio vaccine)
• Replaces old schedule for just oral vaccines

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Risks from administration of polio vaccine

• Vaccine( OPV) causes 8-10 cases of paralysis a
  year
• Paralysis is transitory in most
• Replicates in gastric mucosa and if it sustains
  mutations it can cause disease
• IPV - no serious side effects

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MMR

• Measles, mumps, rubella vaccine
• Deaths from measles has dropped from 3000 a year
  to almost none
• Fever and rash are the most common side effects

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Mumps

• Paramyxovirus
• Transmitted via aerosolized droplets
• Infects the parotid glands in the neck( enters
  through the ducts of the salivary glands)
• Causes fever, extreme swelling of the neck. The
  neck becomes very hard
• It used to be one of the major causes of
  meningitis prior to the development of the
  vaccine

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Swollen Parotid Glands
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Measles

• Before the vaccine there were 3-4 million cases
  of measles per year
• There were 3000 deaths
• Since 1995 there have been no deaths
• 240 million doses of the vaccine and no
  significant problems

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Measles

• Measles, also called Rubeola, is a highly
  contagious - but rare - respiratory infection
  that's caused by a virus.
• It causes a total-body skin rash and flu-like
  symptoms, including a fever, cough, and runny
  nose.

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Worldwide Immunization
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Comparison of cases of Measles
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Side Effects of Vaccine

• Rash
• Fever of 103oF
• Measles vaccine is grown in eggs it represents a
  problem for people with egg allergies

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Initial vaccination

• First immunization given between 12-15 months
• Second shot given at 4-6 years
• Boosters may be given before entry to college

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Rubella German Measles

• Rubella -commonly known as German measles or
  3-day measles
• It is an infection that primarily affects the
  skin and lymph nodes. It is caused by the rubella
  virus

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Teratogenic virus

• 85 of women infected with Rubella in the first
  trimester of pregnancy have children with severe
  birth defects
• Children are born with blindness, deafness, and
  severe heart defects

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Rubella titer

• Women of reproductive age if planning a pregnancy
  should have a blood test to determine their
  status
• Rubella titers measure the antibody level in the
  blood

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Rubella
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Hib Vaccine for Haemophilus influenza

• Haemophilius influenza type B
• Licensed for use in children under the age of 5
  years old
• Mild symptoms
• Redness around the injection site
• Low grade fever
• For many years it was believed that bactericidal
  antibody directed against PRP capsule ofH.
  influenzae type b was entirely responsible for
  host resistance to infection.

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Effects of Haemophilus influenza

• High Fever
• Swollen lymph nodes
• Headache
• Drowsiness
• Irritability
• Epigottitis
• Osteomyelitis
• Meningitis

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Pathogenicity

• For many years it was believed that bactericidal
  antibody directed against PRP capsule of H.
  influenzae type b was entirely responsible for
  host resistance to infection.

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Vaccine type

• Conjugate vaccine made by binding a
  polysaccharide to a protein

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Hib vaccine in the Americas
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Comparison of vaccinated and non vaccinated
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Hepatitis B

• 300,000 people in the United States are infected
  with Hepatitis B
• Affects the liver and can cause cirrhosis
• Can also lead to liver cancer
• Vaccine has had a significant impact
• 10 million people have been vaccinated

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Transmission

• Sexual contact
• Breast milk
• Serum ( used to be called serum Hepatitis

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Immune Response to Hepatitis B

• Virions consist of an outer lipid envelope and an
  icosahedal core, the latter being composed of
  both protein and DNA.
• The outer envelope contains embedded proteins
  which are involved in viral binding of, and
  release into, susceptible cells.
• Virion shape is generally spherical with a
  diameter of 40 - 48 nanometers (nm) but
  pleomorphic forms exist, including filamentous
  and spherical bodies lacking a core. These
  "subviral" particles are not infectious

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Hepatitis B Symptoms
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Cycle

• Upon entry into a host cell, the virus'
  double-stranded DNA genome is relocated to the
  cell's nucleus and converted to covalently closed
  circular DNA form, from which viral mRNAs are
  transcribed
• These transcripts are exported to cytoplasm for
  translation of the envelope proteins (also known
  as hepatitis B surface antigen, or HBsAg),
  hepatitis B e antigen (HBeAg), and the X protein,
  whose function is still under debate
• A fourth pre-genomic RNA is transcribed, which
  translates the polymerase and core proteins.
• Polymerase and pre-genomic RNA are encapsidated
  in the assembling core particles, where reverse
  transcription of the pre-genomic RNA to genomic
  DNA occurs by the Reverse Transcriptase (RT)
  protein. The mature core particle then exits the
  cell via normal secretory pathway, acquiring an
  envelope along the way.

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Antigens
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Cirrhosis of the liver
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World Wide Distribution of surface antigen
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Hepatavax

• Purified (!) HBsAg from the blood of chronic
  carriers has been used as a vaccine since 1981
  (Hepatavax-B) and continues to be used in some
  areas of the world. Recombinant HBsAg vaccines
  produced in yeast have been available since 1986
  and are now most widely used (e.g. Engerix-B,
  Recombivax-HB), e.g. part of the W.H.O. expanded
  program on immunization. A combined hepatitis A
  and B vaccine (Twinrix - GlaxoSmithKline
  Biologicals) is now licenced for use in persons
  aged 18 years. This consists of the antigenic
  components used in Havrix (HAV) and Engerix-B
  (HBV) vaccines. These are vaccines are safe and
  effective - one of the few recombinant vaccines
  to date. Effective vaccination campaigns could

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New Research

• Lamivudine (3TC - 2'deoxy, 3'thiacytidine - a
  reverse transcriptase inhibitor) is currently
  being investigated for therapy of chronic HBV
  infection. Early results suggest this drug may be
  effective in patients who have previously failed
  to clear the virus with a-IFN.A number of other
  nucleoside and nucleotide analogues are now known
  to inhibit HBV replication in vitro and in vivo,
  including penciclovir, lobucavir and adefovir

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Rotavirus Infant Diarrhea inThird World
Countries