RESEARCH SUMMARY Q7
Biomedical evidence in practice
Radboud University, Nijmegen
Made by: Georgia Graat
,Research summary Q7
Module vaccinations
Vaccine program and concept of vaccination
The RIVM and health minister have decided on the Dutch national immunization program
(Rijksvaccinatie program) containing all the vaccines children receive. Children <18 receive 12
vaccinations against harmful infectious diseases. Some are given at a very young age, as those
diseases are more harmful and even lethal earlier in life, which is also the age children get the
disease. The program is set up as follows:
• DKTP-Hib-HepB vaccination (combination of 6)
Given at 3, 5 and 11 months (booster vaccination). It protects
against diphtheria (disease of throat), whooping cough,
tetanus, polio, Hib-diseases (pneumonia, meningitis and
arthritis) and hepatitis B. The vaccine is build up of the toxins
of the diphtheria bacteria, parts of the whooping cough
bacteria, parts of the three different polio viruses, parts of the
Hib bacteria, toxins of the tetanus bacteria and hepatitis B
surface antigens with DNA. On the right, you can see how the
composition is described, which antigens/strains are present
and in which amounts.
There is also a DKTP booster vaccination at 4 years and a DTP
booster vaccination at 9 years. These should together provide
live-long immunization. Still, the vaccination is given again
when you have a big wound with dirt or travel to a non-Western country.
• PNEU vaccination
Given at 3, 5 and 11 months (booster vaccination). This protects against the 10 most prevalent
pneumococci. The vaccine contains parts of the pneumococci.
• BMR vaccination
Given at 14 months and 9 years (booster vaccination). It protects against the mumps, measles and
rubella (bof, mazelen en rode hond). It contains weakened viruses of all three diseases.
• MenACWY vaccination
Given at 14 months and 14 years (booster vaccination). This protects against meningococcus bacteria
A, C, W and Y. It contains parts of the meningococcus bacteria itself.
• HPV vaccination
Given at 13 years twice (booster vaccination), for now only to girls. It protects against the human
papilloma virus type 16 and 18 (most prevalent viruses causing cervical cancer). It contains DNA and
other parts of the HPV virus.
• 22 week vaccination
Given to pregnant women. It protects against whooping cough, for mother as well as fetus
(immunoglobins through placenta). It contains parts of the whooping cough bacteria.
Made by: Georgia Graat
,Vaccinations are actually the most effective medical intervention ever introduced, as they 1)
promote health by keeping people healthy, 2) have an expansive reach over the entire population, 3)
save lives and costs by mortality and hospitalization and 4) have rapid impact upon introduction.
Vaccines are therefore needed nowadays to eradicate diseases and keep people healthy.
Variolation means putting the actual virus/bacteria in
someone, causing them to build resistance but also to get sick
of the disease. Vaccination means putting something similar
to the virus/bacteria in someone, causing them to only build
resistance against the disease. The concept behind
vaccination is that people build an immune system response
against a certain virus/bacteria and therefore become
resistant. This means they will get less sick and eliminate the
particles from the body faster when they obtain the
virus/bacteria later in life. This is because the vaccine has
already induced the slow and relatively weak primary immune
response, but still gives protection via memory cells. The secondary immune response by a booster
or infection is way faster and stronger, as the memory cells cause an influx of antibodies.
Organization of a new vaccine
A vaccine is a biological preparation that improves immunity to a particular
disease. It typically contains an agent that resembles a disease-causing micro-
organism and is made from weakened or killed microbes, its toxins or other
purified components. The agent stimulates the body’s immune system to
recognize it as foreign, destroy it and remember it. The immune system can then
more easily recognize and destroy any of the real micro-organisms that it
encounters later in life.
The first vaccine introduced was for small pox. This was developed with an aged
bacterial culture put into a chicken, causing it to obtain immunization. This caused
it to be resistant against the fresh bacterial culture, that normally killed other
chickens. There came many more vaccines after each other. Nowadays, we know
more about vaccinations and we tend to look more into the importance and side
effects.
A vaccine actually has the same reaction as a naturally occurring infection; both cause immunization
and thus immunity (long-term protection). An advantage is when vaccinating, you don’t have to
endure the actual disease. The low risk of adverse reactions also outweigh the risk of complications
during natural infection. Nowadays, we develop new vaccines for diseases that are very infectious
and/or kill a lot of people.
The actual production of a vaccine in the preclinical phase usually takes several years. The trial steps
in production are: protocol development, consent procedure, standard operating procedures, ethics
approval, regulatory approval, monitoring for GCP adherence, logistics and organization and data
management. Next to the development of the antigens and substrates, lab studies like animal and
model testing are needed to show efficacy. The two initial requirements before testing a vaccine in
clinical trials: must have 100% protection in non-human primates and GMP production is available on
a large scale.
Made by: Georgia Graat
, When the vaccine has been developed, it undergoes three
different clinical trial phases. These all have to be walked through
properly before implementation can occur. The first phase only
includes a low-risk, small sample size to test for safety,
tolerability/adverse events and immunogenicity for only several
days-weeks. The second phase includes a larger sample size to
test for safety, adverse events, immune response and optimal
dosage for weeks-months. The third phase has a large sample
size followed for a longer time (years) to look at efficacy and
safety.
The third phase is a typical efficacy trial with high costs. The
control group is chosen as placebo, vaccine for other disease or
other vaccine for this disease. You calculate the vaccine efficacy
as (risk control group – risk intervention group / risk control
group). The VE is wanted around 95%, but you can deviate from
this if the disease burden is very high or when there are no
alternatives.
Phase 4 is the post-licensure surveillance, where the vaccine is already in use in the general
population and individuals are no longer observed in clinical trials. Large numbers of people are
being vaccinated, also those originally excluded from the clinical trials. There are other factors
causing AEFI’s (incorrect administration) that have to be monitored for safety and the rare adverse
vaccine reactions become visible. Phase 4 is useful to check for all types of adverse events over a
longer time period and the efficacy on the spread of the disease (the ability to protect from illness).
When one of these aspects is poor, the vaccine can still be pulled from the market.
Health council and public acceptance
The health council is an independent, scientific advisory organ for the government. They will look
into all new vaccines on the market and give an advice to the minister if these should be admitted in
the Dutch national vaccination program. If so, they will also give advice on how, why, when to
implement it, amount of booster, who to give it to etc. They always look what has the most benefit
for the general population, by protecting them at the same time from disease and harmful vaccines.
If the benefits and risks are not balanced (especially in low-demanding diseases), the council will give
a negative advice for implementation. The minister of health eventually decides on admission in the
Rijksvaccinatie program or not. The vaccine is also already available on the market, so the population
is able to take it individually.
The health council has specific criteria for the evaluation of including a vaccine in the program.
Application of these criteria is through expert judgement of weighing qualitative and quantitative
pros and cons. Critical appraisal of scientific evidence is necessary. The first four points are the
‘’technical evaluation’’, which are the most important.
1. Disease burden
It should cause serious health issues for individuals as well as (potentially) large numbers of
infections and health issues in the population.
2. Effectiveness/efficacy
Made by: Georgia Graat
Biomedical evidence in practice
Radboud University, Nijmegen
Made by: Georgia Graat
,Research summary Q7
Module vaccinations
Vaccine program and concept of vaccination
The RIVM and health minister have decided on the Dutch national immunization program
(Rijksvaccinatie program) containing all the vaccines children receive. Children <18 receive 12
vaccinations against harmful infectious diseases. Some are given at a very young age, as those
diseases are more harmful and even lethal earlier in life, which is also the age children get the
disease. The program is set up as follows:
• DKTP-Hib-HepB vaccination (combination of 6)
Given at 3, 5 and 11 months (booster vaccination). It protects
against diphtheria (disease of throat), whooping cough,
tetanus, polio, Hib-diseases (pneumonia, meningitis and
arthritis) and hepatitis B. The vaccine is build up of the toxins
of the diphtheria bacteria, parts of the whooping cough
bacteria, parts of the three different polio viruses, parts of the
Hib bacteria, toxins of the tetanus bacteria and hepatitis B
surface antigens with DNA. On the right, you can see how the
composition is described, which antigens/strains are present
and in which amounts.
There is also a DKTP booster vaccination at 4 years and a DTP
booster vaccination at 9 years. These should together provide
live-long immunization. Still, the vaccination is given again
when you have a big wound with dirt or travel to a non-Western country.
• PNEU vaccination
Given at 3, 5 and 11 months (booster vaccination). This protects against the 10 most prevalent
pneumococci. The vaccine contains parts of the pneumococci.
• BMR vaccination
Given at 14 months and 9 years (booster vaccination). It protects against the mumps, measles and
rubella (bof, mazelen en rode hond). It contains weakened viruses of all three diseases.
• MenACWY vaccination
Given at 14 months and 14 years (booster vaccination). This protects against meningococcus bacteria
A, C, W and Y. It contains parts of the meningococcus bacteria itself.
• HPV vaccination
Given at 13 years twice (booster vaccination), for now only to girls. It protects against the human
papilloma virus type 16 and 18 (most prevalent viruses causing cervical cancer). It contains DNA and
other parts of the HPV virus.
• 22 week vaccination
Given to pregnant women. It protects against whooping cough, for mother as well as fetus
(immunoglobins through placenta). It contains parts of the whooping cough bacteria.
Made by: Georgia Graat
,Vaccinations are actually the most effective medical intervention ever introduced, as they 1)
promote health by keeping people healthy, 2) have an expansive reach over the entire population, 3)
save lives and costs by mortality and hospitalization and 4) have rapid impact upon introduction.
Vaccines are therefore needed nowadays to eradicate diseases and keep people healthy.
Variolation means putting the actual virus/bacteria in
someone, causing them to build resistance but also to get sick
of the disease. Vaccination means putting something similar
to the virus/bacteria in someone, causing them to only build
resistance against the disease. The concept behind
vaccination is that people build an immune system response
against a certain virus/bacteria and therefore become
resistant. This means they will get less sick and eliminate the
particles from the body faster when they obtain the
virus/bacteria later in life. This is because the vaccine has
already induced the slow and relatively weak primary immune
response, but still gives protection via memory cells. The secondary immune response by a booster
or infection is way faster and stronger, as the memory cells cause an influx of antibodies.
Organization of a new vaccine
A vaccine is a biological preparation that improves immunity to a particular
disease. It typically contains an agent that resembles a disease-causing micro-
organism and is made from weakened or killed microbes, its toxins or other
purified components. The agent stimulates the body’s immune system to
recognize it as foreign, destroy it and remember it. The immune system can then
more easily recognize and destroy any of the real micro-organisms that it
encounters later in life.
The first vaccine introduced was for small pox. This was developed with an aged
bacterial culture put into a chicken, causing it to obtain immunization. This caused
it to be resistant against the fresh bacterial culture, that normally killed other
chickens. There came many more vaccines after each other. Nowadays, we know
more about vaccinations and we tend to look more into the importance and side
effects.
A vaccine actually has the same reaction as a naturally occurring infection; both cause immunization
and thus immunity (long-term protection). An advantage is when vaccinating, you don’t have to
endure the actual disease. The low risk of adverse reactions also outweigh the risk of complications
during natural infection. Nowadays, we develop new vaccines for diseases that are very infectious
and/or kill a lot of people.
The actual production of a vaccine in the preclinical phase usually takes several years. The trial steps
in production are: protocol development, consent procedure, standard operating procedures, ethics
approval, regulatory approval, monitoring for GCP adherence, logistics and organization and data
management. Next to the development of the antigens and substrates, lab studies like animal and
model testing are needed to show efficacy. The two initial requirements before testing a vaccine in
clinical trials: must have 100% protection in non-human primates and GMP production is available on
a large scale.
Made by: Georgia Graat
, When the vaccine has been developed, it undergoes three
different clinical trial phases. These all have to be walked through
properly before implementation can occur. The first phase only
includes a low-risk, small sample size to test for safety,
tolerability/adverse events and immunogenicity for only several
days-weeks. The second phase includes a larger sample size to
test for safety, adverse events, immune response and optimal
dosage for weeks-months. The third phase has a large sample
size followed for a longer time (years) to look at efficacy and
safety.
The third phase is a typical efficacy trial with high costs. The
control group is chosen as placebo, vaccine for other disease or
other vaccine for this disease. You calculate the vaccine efficacy
as (risk control group – risk intervention group / risk control
group). The VE is wanted around 95%, but you can deviate from
this if the disease burden is very high or when there are no
alternatives.
Phase 4 is the post-licensure surveillance, where the vaccine is already in use in the general
population and individuals are no longer observed in clinical trials. Large numbers of people are
being vaccinated, also those originally excluded from the clinical trials. There are other factors
causing AEFI’s (incorrect administration) that have to be monitored for safety and the rare adverse
vaccine reactions become visible. Phase 4 is useful to check for all types of adverse events over a
longer time period and the efficacy on the spread of the disease (the ability to protect from illness).
When one of these aspects is poor, the vaccine can still be pulled from the market.
Health council and public acceptance
The health council is an independent, scientific advisory organ for the government. They will look
into all new vaccines on the market and give an advice to the minister if these should be admitted in
the Dutch national vaccination program. If so, they will also give advice on how, why, when to
implement it, amount of booster, who to give it to etc. They always look what has the most benefit
for the general population, by protecting them at the same time from disease and harmful vaccines.
If the benefits and risks are not balanced (especially in low-demanding diseases), the council will give
a negative advice for implementation. The minister of health eventually decides on admission in the
Rijksvaccinatie program or not. The vaccine is also already available on the market, so the population
is able to take it individually.
The health council has specific criteria for the evaluation of including a vaccine in the program.
Application of these criteria is through expert judgement of weighing qualitative and quantitative
pros and cons. Critical appraisal of scientific evidence is necessary. The first four points are the
‘’technical evaluation’’, which are the most important.
1. Disease burden
It should cause serious health issues for individuals as well as (potentially) large numbers of
infections and health issues in the population.
2. Effectiveness/efficacy
Made by: Georgia Graat
