Transcript Document
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 4.
5.
6.
Many challenges still to be solved 1.
Emerging & re-emerging infections 2.
3.
Antigenic variation Societal impact of vaccines Opposition to vaccines Safety & risk Poverty related disease 1 Rembrandt van Rijn. The Rat Catcher (1632)
1.
Emerging & re appearing
infectious disease
During the 20th century, infectious diseases remain among the leading causes of death worldwide for three reasons: (1) (2) (3) emergence of
new
infectious diseases re-emergence of
old
infectious diseases persistence of
intractable
infectious diseases 2
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
pathogens. to bring people into closer and more
frequent contact
with Vaccines for these disease will take time to develop & license 4
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 5
Antigenic variation
widespread is
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 7
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
infection of 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 full-blown disease
of the real impact of the 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 10
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
maintenance of confidence and sufficient vaccination coverage to provide herd immunity is very important to the The development of vaccines has reached a high level of complexity where safety concerns need to be addressed correctly 11
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 12
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 events
Frequency of some scientifically proven serious reactions to vaccines All
Vaccine Reaction
Anaphylaxis
Frequency
1 :50,000 1,000,000 Oral polio vaccine measles Paralytic polio 1:750,000 (first doses) Thrombocytopenic purpura 1:22,300 15
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 16
Unproven adverse events - associations between vaccine & health conditions
all unproven - some examples of myths believed to be true by public
Health condition
Neurological damage Chronic fatigue syndrome Sudden Infant Death Multiple Sclerosis
Vaccine incriminated
DTP (diphtheria, tetanus, pertussis) Hepatitis B
Source country
Scotland Canada DTP (diphtheria, tetanus, pertussis) Hepatitis B France France Autism Mental retardation MMR (measles, mumps & rubella) Thimerosal (preservative) UK USA 17
Epidemiological studies to investigate suggested associations
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Epidemiological studies to investigate suggested associations 19
6. Poverty related disease
Inequity poverty
in disease burden is related to 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
the population; Smaller, more affordable families High priority for education Savings & investment for the future Longer, productive working lives Lower health costs to 20
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 21
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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 people decide
and
innovates
but 24