Future Challenges for Vaccines

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Future Challenges for Vaccines

• In the short time in human history since vaccines
  have been introduced on a global scale they have
  changed the world

• Many challenges still to be solved
• Emerging re-emerging infections
• Antigenic variation
• Societal impact of vaccines
• Opposition to vaccines
• Safety risk
• Poverty related disease

Rembrandt van Rijn. The Rat Catcher (1632)
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1. Emerging re-appearing infectious disease

• During the 20th century, infectious diseases
  remain among the leading causes of death
  worldwide for three reasons
• emergence of new infectious diseases
• re-emergence of old infectious diseases
• persistence of intractable infectious diseases

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Emerging/Re-emerging Infectious Disease
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New infectious diseases continue to evolve
"emerge.

• Changes in human demographics, behavior, land
  use, etc. are contributing to new disease
  emergence by changing transmission dynamics to
  bring people into closer and more frequent
  contact with pathogens.
• Vaccines for these disease will take time to
  develop license

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2. Antigenic diversity variation

• Antigenic diversity is an escape strategy for
  pathogens to avoid immune responses
• Vaccines must include the diverse antigens to be
  successfully protective
• Antigenic variation in pathogens can occur over
  time. It can be fast or slow and reflect the rate
  of mutation but is a means for avoiding specific
  immunity
• E.g. HIV, Hepatitis C, malaria
• Success of vaccination varies if the pathogens
  antigens change

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Antigenic variation is widespread

• True natural antigenic variation has been
  demonstrated in many pathogens, including
  Neisseria gonorrhoeae, Mycoplasma spp,
  Pneumocystis carinii, and Giardia lamblia.
• The complete genomic sequences of other
  pathogenic bacteria, such as Helicobacter pylori,
  Treponema pallidum, and Mycobacterium
  tuberculosis, includes families of repeated genes
  that are polymorphic in sequence and may be
  involved in antigenic variation.

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Antigenic variation- tricks the host ( vaccine
designer)

• Antigenic variation has important implications
  for the development of vaccine.
• The vaccine needs to be multivalent (directed
  against multiple antigens), perhaps to the point
  of impracticality.
• If the infected host animal has not solved the
  problem of identifying an antigen that is
  conserved among the variants, how can vaccine
  developers hope to do this?
• If variant strains replace the one targeted by
  vaccines then the disease is no longer controlled

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Antigenic variation in influenza A

• Influenza A virus is able to persistently
  re-infect human populations by continually
  evading host immunity through the continuous and
  rapid evolution of surface antigens
  haemagglutinin (H) and neuraminidase(N). This
  process is known as antigenic drift.
• A vaccine directed against one type of influenza
  virus (e.g. H3N2) does not protect against
  infection with a different antigenic type (e.g.
  H5N1).

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3. Societal impact of of vaccines

• Vaccination of a large population can lead to
  protection of the entire population due to the
  herd effect
• Fewer infected people means reduced transmission
  of infection
• Thus wide vaccination cover can protect those who
  are not vaccinated such as very small babies
  because the level of vaccination reduces the risk
  of transmission of the disease.

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4. Opposition to vaccines

• The success of vaccines in controlling
  eliminating childhood infections had led to the
  revival of the anti-vaccination movement.
• Many people have no knowledge or memory of the
  real impact of the full-blown disease
• They do not perceive any risk to them or their
  child for these infections nor value the
  protection of a vaccine
• Their suspicion or belief that the risk of
  adverse events is greater than the risk of
  full-blown disease has led to breakdown of
  confidence

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5. Safety risk

• Immunisation are among the safest most cost
  effective public health interventions
• No vaccine however is completely safe or
  effective
• Close monitoring of adverse events is very
  important to the maintenance of confidence and
  sufficient vaccination coverage to provide herd
  immunity
• The development of vaccines has reached a high
  level of complexity where safety concerns need to
  be addressed correctly

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5. Safety risk

• A great challenge is the need to rapidly and
  cost-effectively determine the safety and
  efficacy of new vaccines
• Vaccine trials are long, complex and expensive.
• Due to these costs some new vaccines appear as
  low-profit products that although useful may
  never be licensed
• The risk of litigation outweighs the cost of
  development
• The public in the developed world requires an
  almost zero-risk product
• For these reason the level of safety requirement
  has increased enormously for new vaccines when
  compared with traditional vaccines
• The time to market and cost of development have
  increased in parallel

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Life Cycle of an immunisation program
5. At this point, most people have not
experienced the disease, and they worry about
about possible side-effects of the vaccine.
People may start to question whether the vaccine
is necessary or safe, and some people will stop
getting immunized. 6. If enough people stop
getting immunized, disease numbers will start to
rise again, and there will be outbreaks. 7.
People are reminded of how bad the disease can
be, and turn back to immunization to avoid it.
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Adverse event reporting in USA

• The Vaccine Adverse Event Reporting System is a
  cooperative program for vaccine safety of the
  Centers for Disease Control and Prevention (CDC)
  and the Food and Drug Administration (FDA). VAERS
  is a post-marketing safety surveillance program,
  collecting information about adverse events
  (possible side effects) that occur after the
  administration of US licensed vaccines.
• This Web site provides a nationwide mechanism by
  which adverse events following immunization
  (AEFI) may be reported, analyzed and made
  available to the public.
• The VAERS Web site also provides a vehicle for
  disseminating vaccine safety-related information
  to parents/guardians, healthcare providers,
  vaccine manufacturers, state vaccine programs,
  and other constituencies.

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Adverse eventsFrequency of some scientifically
proven serious reactions to vaccines
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Real adverse events - errors in manufacture

• Besides the potentially serious reactions caused
  by the vaccines themselves, adverse events due to
  programmatic errors occur. E.g.
• Use of wrong diluent
• Transmission of pathogens due to poor aseptic
  technique
• Incomplete inactivation of virus or bacterium
  (vaccine is virulent)
• Modern methods of manufacture quality control
  (Good Manufacturing Practice/GMP) aim to catch
  these errors before they cause harm

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Unproven adverse events - associations between
vaccine health conditionsall unproven - some
examples of myths believed to be true by public
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Epidemiological studies to investigate suggested
associations
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Epidemiological studies to investigate suggested
associations
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6. Poverty related disease

• Inequity in disease burden is related to poverty
• The healthier a population the more the adults
  can contribute to productive activity and
  children are brought up in a stable environment
• Income is directly related to health
• Fertility
• Education
• Productivity
• Strategies such as vaccination that sustain good
  health promote non-medical benefits to the
  population
• Smaller, more affordable families
• High priority for education
• Savings investment for the future
• Longer, productive working lives
• Lower health costs

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6. Poverty related diseases

• implementation of sustainable vaccination
  programs in poor countries remains a problem
• Cost
• Social disruption (eg AIDS affected adults)
• Logistical difficulty (infrastructure,
  cold-chain, trained staff)
• Poor governance (lack of management,
  record-keeping)
• Instability (war and disaster)
• Global Alliance for Vaccination Immunization
  (GAVI) is an alliance of financiers, vaccine
  developers manufacturers, governments, agencies
  (UNICEF, WHO) and donors (Bill Melinda Gates
  Foundation) to collectively fund solve some of
  these problems

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Challenge for relevant use of vaccines in the
future

• Better information and communication are the keys
  to relevant use of vaccines
• For individuals
• For parents
• For health professionals
• For bureaucrats
• For governments
• For transnational health agencies
• For major donors
• Science informs and innovates but people decide