Vaccination

• Immunisation


  Latin meaning exempt, if you recover you never get it again
• Thucydides 430BC, Athens Plague - only recovered people nurse the sick
• 15th Century China/Aztecs, inhaled crusts of smallpox to provide protection
• Jenner 18th C, cowpox can provide immunity against smallpox, VACCINATION discovered
• Pasteur 19th C, attenuated rabies virus used as a vaccine, VACCINATION improved
• Vaccines


  Contain antigens found on pathogens causing disease but exposure to these antigens in the vaccine does not cause disease
• Antibody response


  1. Primary antibody response

  2. Secondary antibody response
• Vaccination


  Refers to having received the vaccine i.e. getting the injection
• Immunisation


  Means both receiving a vaccine and becoming immune to a disease, as a result of being vaccinated
• Vaccines


  • Induce active immunity - induces immunity and immunologic memory similar to that acquired by exposure to natural infection but without the risk of disease
  • Induce immunological memory - allows rapid recognition and response to infection; prevents or modifies effects of disease
• Innate Immunity


  Resistance to infection NOT improved by repeated infection: Complement, Phagocytes, Natural killer cells
• Acquired or Adaptive Immunity

  Resistance IS improved by repeated infection: Antibody, T cells
• Vaccination success 1: incidence of viral diseases in the USA

  • Measles
  • Other viral diseases
• Vaccination success 2: measles in England and Wales


  • Incidence and deaths
• Requirements of a good vaccine

  • Elicit a response that gives same immune protection that usually follows natural infection - but without causing disease
  • Safe - no side effects or contraindications
  • Stability - no requirement for 'cold chain' storage
  • Cost - cannot be too high for use in developing countries
  • Ease of administration - oral vs injection
  • Long term protection (single shot)
  • Interrupt spread of infection
• Types of vaccine


  • Live vaccines - whole pathogen (bacteria or viruses) for which virulence has been artificially reduced = attenuation
  • Inactivated vaccines - whole "killed" organisms
  • Subunit vaccines - certain components of pathogens; now often generated using recombinant DNA technology
  • Toxoid vaccines
  • Surface protein vaccines
  • Viral vector vaccines
  • DNA & RNA vaccines
  • Passive immunotherapy
• Poliomyelitis


  Viral disease that mainly affects children < 5 years of age, 1 in 200 infections result in irreversible paralysis - 5-10% of those affected by paralysis die when muscles aiding breathing are immobilised
• Polio cases have decreased by >99.9% since 1988, in 2017 only 3 countries (Afghanistan, Nigeria and Pakistan) remained polio-endemic (in 1988 was >125 countries)
• WHO estimates ~1.5 million childhood deaths prevented by vaccination and predicts eradication of polio would save US$ 40–50 billion (1988 to 2035) - mostly in low-income countries
• Poliovirus


  3 different serotypes: Type I - Brunhilde, Type II - Lansing, Type III - Leon, the disease caused by the different serotypes is indistinguishable but antibodies produced against one serotype do not provide protection against other serotypes
• Live attenuated oral vaccine (OPV or Sabin)

  Live attenuated polio vaccine originally produced by allowing polio virus to grow in non-optimal conditions and selecting randomly occurring mutants that had lost neuro-virulence
• Advantages of live attenuated vaccine

  • Inexpensive and easily administered - supplied as a single oral dose (costs less than US$0.15 per dose)
  • Induces both systemic and mucosal immunity
  • Antibodies in blood prevent spread of poliovirus to CNS
  • Mucosal immune response prevents viral replication in gut and interrupts poliovirus transmission
  • Potent response resembles optimal naturally acquired immune response
  • Short-term shedding of OPV in faeces can result in passive immunisation of persons in close contact
  • Immunity is probably life long
• Disadvantages of live attenuated vaccine

  • May reproduce features of the disease as subclinical or mild form of the infection
  • Cannot be given to immunosuppressed or pregnant patients
  • Unstable - 12 months at 4°C, 6 weeks at 25°C, 1 week at 37°C
  • May revert to virulent form (e.g. neuro-virulence) - Type 1 has 57 different base substitutions, Types 2 & 3 have 2 base substitutions related to loss of virulence
• Vaccine-derived poliovirus (cVDPV)


  Type 1: 100% of 2014 wild cases, Type 1: 8% of cVDPV, Type 2: Eradicated in 1999, Type 2: 90% of cVDPV, Type 3: Last seen in 2012, Type 3: 2% of cVDPV
• In 2014, 52 cases of polio were due to circulating vaccine-derived poliovirus (cVDPV) compared to 358 wild polio virus cases
• Inactivated Polio Vaccine (Salk)

  Consists of 3 serotypes - chemically inactivated, cannot cause cVDPV, antibodies prevent spread of poliovirus to CNS, administered as a sub-cutaneous injection (higher cost, starting at US$1 per dose for low-income countries), no effect on viral replication in the gut or viral transmission in stool - protects the individual but as wild polio virus can replicate in gut wild virus can be spread to infect others
• Advantages of inactive vaccines

  • Cannot cause infection
  • Can be given to immunosuppressed and pregnant individuals
• Disadvantages of inactive vaccines

  • Less immunogenic and require addition of adjuvants and booster doses
• Unlike most diseases, polio can be completely eradicated as poliovirus cannot survive for long periods outside of the human body, Type 2 eradicated (1999) and Type 3 eradicated (2019)
• Eradication campaign being compromised in Pakistan and Afghanistan - Taliban targeting workers carrying out polio vaccination programme - children were not being immunised (2018- Nov 2021) and polio cases rose
• Adjuvant


  To enhance immune response to the antigens included in the vaccine, mode of actions not precisely defined: to carry the vaccine antigen and slow its release, to provoke a local inflammatory response, an example is aluminium hydroxide (Alum)
• Toxoid vaccines


  For diseases that are caused solely through production of toxins - possible to vaccinate against a 'detoxified' version of the toxin, immunisation allows body to neutralise the toxin, and so prevent disease, with the immune system eliminating the pathogen, to prevent toxic effect of toxin requires chemical inactivation to remove toxicity but it is essential that it retains antigenicity
• Examples of toxoid vaccines - diptheria, tetanus, pertussis = whooping cough; all bacterial infections
• Tetanus


  Caused by the bacterium Clostridium tetani, spores of this bacterium are widespread in the environment, tetanus is caused by a neurotoxin produced when C. tetani grows in
• Attenuation


  Artificial reduction of virulence of pathogens (bacteria or viruses)
• Types of vaccines


  • Inactivated vaccines
  • Subunit vaccines
  • Toxoid vaccines
  • Surface protein vaccines
  • Viral vector vaccines
  • DNA & RNA vaccines
  • Passive immunotherapy
• Adjuvant


  Enhances immune response to the antigens included in the vaccine
• Adjuvant mode of action

  • Carries the vaccine antigen and slows its release
  • Provokes a local inflammatory response
• Adjuvant


  • Aluminium hydroxide (Alum)
• Toxoid vaccines


  For diseases caused solely through production of toxins - possible to vaccinate against a 'detoxified' version of the toxin