Novel Vaccine Technologies and Applications
1. A (short) history of vaccination 28/02
Vaccines are a ‘recent invention’ compared the thousands of years that humans have suffered from
major epidemics. Vaccination only started to be effectively used in the 20th century in a structured
manner. Right now there are:
1. Several vaccines developed
2. Routine vaccinations introduced
3. Large populations vaccinated
With the exception of safe water, no other intervention, not even antibiotics, has had such a major
effect on mortality reduction and population growth
1.1 Epidemics & pandemics
The Plague / black death with huge outbreaks around 1700 caused
half the population of Europe to die. Also the Roman Empire
crumbled probably because of a plague outbreak. They already
knew a lot about infectious diseases and took note of mortality
numbers etc., but there were very limited interventions possible.
Around 1889 there was a big Russian Flu epidemic. Now it seems
this pandemic was not the flu but probably a coronavirus epidemic.
Major plagues only started occurring since around 1350, because
people started trading and traveling a lot. Links between people and
continents are ideal for pathogens to spread. When before 1350
zoonotic pathogens jumped to people, it usually remained in one
city. Here all people possibly died but it did not spread further.
Vaccines are a ‘recent invention’: before vaccines…
Before vaccines, the practice of quarantine already started during the 14th century to protect coastal
cities from plague epidemics. Port authorities required ships arriving in Venice from infected ports to
sit at anchor for 40 days before landing. The origin of the word quarantine is from the Italian “quaranta
giorni”; or 40 days.
One of the first instances of relying on geography and statistical analysis was in mid-19th century
London, during a cholera outbreak. In 1854, Dr. John Snow came to the conclusion that cholera was
spreading via tainted water and decided to display neighbourhood mortality data directly on a map.
This method revealed a cluster of cases around a specific water pump.
Pagina 1 van 94
, The origin of variolation
Smallpox and variolation
Many people died of smallpox, but some recovered. These recovered individuals then
remained healthy in subsequent outbreaks: they had developed immunity. In the 12th century
this was observed by the Chinese: recovered people are resistant to infection in new outbreaks.
- Infants who survived the resulting disease were protected from smallpox in later life
- Using scabs from mild smallpox cases minimized mortality -> 1% compared with ± 20%
o = inoculation/variolation: deliberate infection with smallpox by inserting scabs from
infected individuals into small cuts in their skin
➔ The knowledge of variolation spread westward to Europe by the early 18th century
The precise origin of variolation remains unknown. It seems to have developed somewhere in Central
Asia around the 12th century. In the 16th century, Brahmin Hindus in India practiced a form of
variolation by introducing dried pus from smallpox pustules into the skin of a patient. The Golden
Mirror of Medicine, a medical text dated 1742, listed four forms of inoculation against smallpox
practiced in China since 1695:
1. The nose plugged with powdered scabs laid on cotton wool
2. Powdered scabs blown into the nose
3. The undergarments of an infected child put on a healthy child for several days
4. A piece of cotton smeared with the contents of a vesicle and stuffed into the nose
Variolation was introduced into England by Lady Mary Wortley Montagu in 1721, after her return from
Constantinople. While living in Turkey, she frequently observed variolation and had her own son
variolated. Dr. Charles Maitland, who performed the procedure on her son, later performed the first
variolation in England on Lady Montagu’s daughter. The treatment was effective, but results were
erratic and 2-3% of persons treated died of smallpox contracted from the variolation itself.
Rinderpest – cattle plague (1754)
- No cure, but inoculation tried: placing bits of material previously dipped
in morbid discharge into an incision in dewlap
o Worked, but not always and not without risk
o Disastrous results in NL -> interest in inoculation declined sharply across the country
- General principles of inoculation were accepted BUT nobody had an idea how it worked
Benjamin Jesty (1774)
Cattle breeder Benjamin Jesty was immune to smallpox after contracting cowpox from his herd. Like
many country farmers in the area, he knew dairymaids seemed to be protected from smallpox after
having contracted cowpox. He deliberately inoculated his wife and children with cowpox to avoid a
smallpox epidemic. He took his wife and children to a nearby field where he knew he could find cattle
with cowpox and inoculated them. His experiment succeeded; they were unaffected by the outbreak.
Jesty’s actions constituted the first known real vaccine—the use of cowpox to protect against
smallpox.
Pagina 2 van 94
1. A (short) history of vaccination 28/02
Vaccines are a ‘recent invention’ compared the thousands of years that humans have suffered from
major epidemics. Vaccination only started to be effectively used in the 20th century in a structured
manner. Right now there are:
1. Several vaccines developed
2. Routine vaccinations introduced
3. Large populations vaccinated
With the exception of safe water, no other intervention, not even antibiotics, has had such a major
effect on mortality reduction and population growth
1.1 Epidemics & pandemics
The Plague / black death with huge outbreaks around 1700 caused
half the population of Europe to die. Also the Roman Empire
crumbled probably because of a plague outbreak. They already
knew a lot about infectious diseases and took note of mortality
numbers etc., but there were very limited interventions possible.
Around 1889 there was a big Russian Flu epidemic. Now it seems
this pandemic was not the flu but probably a coronavirus epidemic.
Major plagues only started occurring since around 1350, because
people started trading and traveling a lot. Links between people and
continents are ideal for pathogens to spread. When before 1350
zoonotic pathogens jumped to people, it usually remained in one
city. Here all people possibly died but it did not spread further.
Vaccines are a ‘recent invention’: before vaccines…
Before vaccines, the practice of quarantine already started during the 14th century to protect coastal
cities from plague epidemics. Port authorities required ships arriving in Venice from infected ports to
sit at anchor for 40 days before landing. The origin of the word quarantine is from the Italian “quaranta
giorni”; or 40 days.
One of the first instances of relying on geography and statistical analysis was in mid-19th century
London, during a cholera outbreak. In 1854, Dr. John Snow came to the conclusion that cholera was
spreading via tainted water and decided to display neighbourhood mortality data directly on a map.
This method revealed a cluster of cases around a specific water pump.
Pagina 1 van 94
, The origin of variolation
Smallpox and variolation
Many people died of smallpox, but some recovered. These recovered individuals then
remained healthy in subsequent outbreaks: they had developed immunity. In the 12th century
this was observed by the Chinese: recovered people are resistant to infection in new outbreaks.
- Infants who survived the resulting disease were protected from smallpox in later life
- Using scabs from mild smallpox cases minimized mortality -> 1% compared with ± 20%
o = inoculation/variolation: deliberate infection with smallpox by inserting scabs from
infected individuals into small cuts in their skin
➔ The knowledge of variolation spread westward to Europe by the early 18th century
The precise origin of variolation remains unknown. It seems to have developed somewhere in Central
Asia around the 12th century. In the 16th century, Brahmin Hindus in India practiced a form of
variolation by introducing dried pus from smallpox pustules into the skin of a patient. The Golden
Mirror of Medicine, a medical text dated 1742, listed four forms of inoculation against smallpox
practiced in China since 1695:
1. The nose plugged with powdered scabs laid on cotton wool
2. Powdered scabs blown into the nose
3. The undergarments of an infected child put on a healthy child for several days
4. A piece of cotton smeared with the contents of a vesicle and stuffed into the nose
Variolation was introduced into England by Lady Mary Wortley Montagu in 1721, after her return from
Constantinople. While living in Turkey, she frequently observed variolation and had her own son
variolated. Dr. Charles Maitland, who performed the procedure on her son, later performed the first
variolation in England on Lady Montagu’s daughter. The treatment was effective, but results were
erratic and 2-3% of persons treated died of smallpox contracted from the variolation itself.
Rinderpest – cattle plague (1754)
- No cure, but inoculation tried: placing bits of material previously dipped
in morbid discharge into an incision in dewlap
o Worked, but not always and not without risk
o Disastrous results in NL -> interest in inoculation declined sharply across the country
- General principles of inoculation were accepted BUT nobody had an idea how it worked
Benjamin Jesty (1774)
Cattle breeder Benjamin Jesty was immune to smallpox after contracting cowpox from his herd. Like
many country farmers in the area, he knew dairymaids seemed to be protected from smallpox after
having contracted cowpox. He deliberately inoculated his wife and children with cowpox to avoid a
smallpox epidemic. He took his wife and children to a nearby field where he knew he could find cattle
with cowpox and inoculated them. His experiment succeeded; they were unaffected by the outbreak.
Jesty’s actions constituted the first known real vaccine—the use of cowpox to protect against
smallpox.
Pagina 2 van 94
