Download Antigenic variation

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
1. Emerging & re-emerging infections
2. Antigenic variation
3. Societal impact of vaccines
4. Opposition to vaccines
5. Safety & risk
6. Poverty related disease
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Rembrandt van Rijn. The Rat Catcher (1632)
1. Emerging & reappearing infectious
disease
 During the 20th century, infectious diseases remain among
the leading causes of death worldwide for three reasons:
(1) emergence of new infectious diseases
(2) re-emergence of old infectious diseases
(3) 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 pathogen’s 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 variationtricks 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
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immunization to avoid it.
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
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constituencies.
Adverse events
Frequency of some scientifically proven serious reactions to vaccines
Vaccine
Reaction
Frequency
All
Anaphylaxis
1 :50,000 1,000,000
Oral polio vaccine
Paralytic polio
1:750,000
(first doses)
measles
Thrombocytopenic 1:22,300
purpura
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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 conditions
all unproven - some examples of myths believed to be true by public
Health
condition
Vaccine
incriminated
Source
country
Neurological
damage
DTP (diphtheria,
Scotland
tetanus, pertussis)
Chronic fatigue
syndrome
Hepatitis B
Sudden Infant
Death
DTP (diphtheria,
France
tetanus, pertussis)
Multiple Sclerosis
Hepatitis B
France
Autism
MMR (measles,
mumps & rubella)
UK
Mental retardation Thimerosal
(preservative)
Canada
USA
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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
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