2025-2026 Vaccine Technologies Peter Delputte
NOVEL VACCINE TECHNOLOGIES AND
APPLICATIONS
INTRODUCTION
A SHORT HISTORY OF VACCINATION
• Vaccines are a ‘recent invention’ compared to the thousands of years that humans have suffered
major epidemics
• Vaccination only started to be effectively used in the 20th century in a structured manner
o Several vaccines developed since
o Routine vaccinations introduced
o Large populations vaccinated
• With the exception of safe water, no other intervention, not even antibiotics, had such a major
effect on mortality reduction and population growth A (short) history of vaccination
• Vaccines are the most controlled intervention in humans, since-we
Epidemics give it to healthy people!
Pandemics
• There have been some huge outbreaks throughout humanity: The Great Plague of London,
Spanish and Russian flu, SARS-CoV-19…
o There’s an introduction of a new pathogen in a population
with no immunity
o A lot of people are killed (steep increase of in deaths)
o The people who survived have immunity (steep decrease in
deaths)
o Epidemic dies out
BEFORE VACCINES
• There was already some knowledge on infectious diseases and protective immunity
o They didn’t know there were pathogens, but they knew that people could get sick in the
vicinity of other sick people
• The practice of quarantine began during the 14th century, to protect coastal cities from plague
epidemics
o Ships arriving in Venice from infected ports needed to sit at anchor for 40 days before
landing
o Quarantine = Quaranta giorni = ’40 days’ in Italian
• One of the first instances of relying on geography and statistical analysis was in mid 19th
century in London, during a cholera outbreak à in 1854 a doctor (John Snow) came to the
conclusion that cholera was spreading via tainted water and decided to display neighborhood
mortality in data directly on a map à revealed a cluster of infections around a specific water
pump à they knew something was up with the water, but were not aware it was a bacterium yet
1
,2025-2026 Vaccine Technologies Peter Delputte
VARIOLATION/INOCULATION
• = no real ‘vaccination’ yet, but it was close
• Many people died of smallpox, but the people that survived and recovered remained healthy in
subsequent outbreaks = they developed immunity
• In China: observed that persons recovered from smallpox were resistant to new outbreaks (in 12th
century) à they started using scabs of the mildest smallpox cases to infect other people by
inoculating/variolating these scabs into small cuts in the skin
• In 16th century: variolation of smallpox in India à introducing dried pus from smallpox pustules
into the skin of a patient
• In 18th century: variolation was documented in China
• In 18th century: variolation was brought in England because Lady Mary Wortley Montagu
frequently observed variolation during her stay in Turkey
• Variolation was effective, but 2-3% died of smallpox contracted from the variolation itself
• The precise origin of variolation remains unknown
FIRST VACCINE
• Vaccine = a biological suspension of a live or inactivated pathogen or fractions/subunits thereof
(i.e. purified protein subunits, conjugated and non-conjugated polysaccharides or split virions)
which can be administered by various routes (IM, SC, ID, oral and intranasal) to induce a specific
long-term immunity (immune memory) and prevent disease caused by a specific pathogen
against which it has been developed.
o ‘Prevent disease’ is not always possible, sometimes it just prevents morbidity/mortality
• Benjamin Jesty was a cattle breeder = he was immune to smallpox after contracting cowpox from
his herd
o He knew that dairymaids seemed to be protected from smallpox after they had
contracted cowpox as well
o He inoculated his wife and children with cowpox to avoid smallpox epidemic =
succeeded
• Jesty’s actions constituted the first known real vaccine – the use of cowpox to protect against
smallpox
• Edward Jenner then did large scale vaccinations with cowpox
o Cowpox was not widespread, so it was difficult to find for use as a vaccine
o They tried to transport cowpox infected cattle (but an infection only lasts for so long) à
we needed susceptible cattle as well à very complex
o They started arm-to-arm transmission (people are easier to transport than cattle) =
providing large-scale inoculation
§ They used orphans/children infected/susceptible to cowpox and brought them
all over the world = seen as hero’s!
o Of course this did not came without risk: this arm-to-arm transmission enhances the
spread of other diseases (like syphilis and tuberculosis)
• The rinderpest was a cattle plague (18th century), for this they also tried inoculation à disastrous
results!
• In 1855, they started to standardize calf-derived vaccines
2
,2025-2026 Vaccine Technologies Peter Delputte
VACCINE TIMELINE
• Louis Pasteur (1879)
o Serendipity = finding something, when looking for something else
o He was investigating fowl cholera (Pasteurella multocida)
A (short) history of vaccination
o Until some student accidentally messed up
§ He forgot to renew Louisthe
Pasteur
bacterial(1879)
culture– serendipity…
over the
weekend = cells died
§ He decided to§use a culture
Louis Pasteur infrom
Francethe week before
investigated fowl (aged
P. multocida) cholera (Pasteurella multocida)
§ He infected a chicken with this culture, but the chicken
§ Accidental aged P. multocida was used, and this
did not die (it was
didhealthy)
not kill chickens, but protected against
§ When a new (fresh) culture
infection with was
fresh given to chickens
P. multocida (Serendipity)
• Chicken previously infected with the aged
culture survived = immunity
• Chickens not previously infected died
• Henry Toussaint (1880)
o Anthrax vaccine 27
o He noted that the blood of bovines, died of anthrax, were full of bacteria
§ He filtered the blood: bacteria could pass through the filter
§ He heated the blood (10min at 55°C to the action of diluted phenol)
à Both techniques resulted in an attenuated vaccine
• At the beginning of 20th century, 5 human vaccines were in use
o Jenner’s original smallpox vaccine
o Pasteur’s rabies vaccine
o 3 bacterial vaccines: typhoid, cholera and plague
o Immunization with diphtheria or tetanus antitoxin was an accepted, unofficial practice!
• At the end of 19th century: the end of arm-to-arm lymph inoculation for smallpox vaccination à
replaced by the use of glycerinated calf lymph in 1898
• End of 19th century: introduction of the fundamental concepts of vaccinology
• Beginning 20th century: refinements to these theoretical underpinnings
o Not until the advent of cell culture 50 years later would the field again become so
dramatically fertile
A (short) history of vaccination
o First animals were used to ‘grow’ viruses, then embryonated chicken eggs were used
Vaccine timeline
32
3
, 2025-2026 Vaccine Technologies Peter Delputte
VACCINES IN THE 20TH CENTURY
• Typhoid vaccines
o Typhoid fever is a bacterial disease caused by Salmonella typhi
o Typhoid fever symptoms are similar to those of other common GI illnesses, including
fever, headache, nausea, constipation or diarrhea, loss of appetite and a rose-colored
rash on the body
o Typhoid fever may lead to intestinal bleeding and perforation, and this may lead to severe
intestinal damage
o Richard Pfeiffer, Wilhelm Kolle and Almroth Wright worked independently on killed
typhoid vaccines
§ Wright proposed ass immunization of British troops with this killed typhoid
vaccine
§ Result was catastrophic: 58,000 typhoid cases with 9000 deaths in the British
army
§ A broad-based trial showed overwhelming effectiveness of the vaccine
• Bacterins
o “bacterins” as human vaccines in early 20th century
o Bacterins = killed bacteria (antigens) injected parentally
o Can be combined with immune serum = serobacterins
o Most bacterins were prepared and sold without clinical trials
o Fell into disuses in late 1930s as more stringent licensing requirements were imposed by
the federal government
• Toxoid vaccines
o Early 20the century: chemical inactivation of diphtheria and other bacterial toxins let to
the development of the first toxoids: diphtheria and tetanus
o 1909: toxoids provide long-lasting immunity against diphtheria in guinea pigs
o 1923: diphtheria toxin could be transformed into a toxoid by formalin, used together with
antitoxin à later, diphtheria toxoid was used on its own (no antitoxin) with adding
formalin = still used
• Rabies
o Rabies = very deadly viral disease of animals and humans
o 1880: Pasteur’s experimental method of attenuation tried on a human disease à efforts
to isolate the rabies virus were unsuccessful (virus remained invisible)
o Passage of rabies virus in animals
§ Inoculation of a part of a dog’s brain into another dog’s brain: inoculated dogs
died à no attenuation, virus remained lethal
§ Serial passage through several rabbits à virus with stable virulence
o Developing a vaccine with attenuated virulence
§ Suspending sections of spinal cord from rabbits inside flasks to dry in a
moisture-free atmosphere
§ Virulence gradually declined until finally disappearing
§ Louis Pasteur injected these spinal cord sections into rabid dogs, followed by
challenge with rabies à no rabies J
o The first live human vaccine
4
NOVEL VACCINE TECHNOLOGIES AND
APPLICATIONS
INTRODUCTION
A SHORT HISTORY OF VACCINATION
• Vaccines are a ‘recent invention’ compared to the thousands of years that humans have suffered
major epidemics
• Vaccination only started to be effectively used in the 20th century in a structured manner
o Several vaccines developed since
o Routine vaccinations introduced
o Large populations vaccinated
• With the exception of safe water, no other intervention, not even antibiotics, had such a major
effect on mortality reduction and population growth A (short) history of vaccination
• Vaccines are the most controlled intervention in humans, since-we
Epidemics give it to healthy people!
Pandemics
• There have been some huge outbreaks throughout humanity: The Great Plague of London,
Spanish and Russian flu, SARS-CoV-19…
o There’s an introduction of a new pathogen in a population
with no immunity
o A lot of people are killed (steep increase of in deaths)
o The people who survived have immunity (steep decrease in
deaths)
o Epidemic dies out
BEFORE VACCINES
• There was already some knowledge on infectious diseases and protective immunity
o They didn’t know there were pathogens, but they knew that people could get sick in the
vicinity of other sick people
• The practice of quarantine began during the 14th century, to protect coastal cities from plague
epidemics
o Ships arriving in Venice from infected ports needed to sit at anchor for 40 days before
landing
o Quarantine = Quaranta giorni = ’40 days’ in Italian
• One of the first instances of relying on geography and statistical analysis was in mid 19th
century in London, during a cholera outbreak à in 1854 a doctor (John Snow) came to the
conclusion that cholera was spreading via tainted water and decided to display neighborhood
mortality in data directly on a map à revealed a cluster of infections around a specific water
pump à they knew something was up with the water, but were not aware it was a bacterium yet
1
,2025-2026 Vaccine Technologies Peter Delputte
VARIOLATION/INOCULATION
• = no real ‘vaccination’ yet, but it was close
• Many people died of smallpox, but the people that survived and recovered remained healthy in
subsequent outbreaks = they developed immunity
• In China: observed that persons recovered from smallpox were resistant to new outbreaks (in 12th
century) à they started using scabs of the mildest smallpox cases to infect other people by
inoculating/variolating these scabs into small cuts in the skin
• In 16th century: variolation of smallpox in India à introducing dried pus from smallpox pustules
into the skin of a patient
• In 18th century: variolation was documented in China
• In 18th century: variolation was brought in England because Lady Mary Wortley Montagu
frequently observed variolation during her stay in Turkey
• Variolation was effective, but 2-3% died of smallpox contracted from the variolation itself
• The precise origin of variolation remains unknown
FIRST VACCINE
• Vaccine = a biological suspension of a live or inactivated pathogen or fractions/subunits thereof
(i.e. purified protein subunits, conjugated and non-conjugated polysaccharides or split virions)
which can be administered by various routes (IM, SC, ID, oral and intranasal) to induce a specific
long-term immunity (immune memory) and prevent disease caused by a specific pathogen
against which it has been developed.
o ‘Prevent disease’ is not always possible, sometimes it just prevents morbidity/mortality
• Benjamin Jesty was a cattle breeder = he was immune to smallpox after contracting cowpox from
his herd
o He knew that dairymaids seemed to be protected from smallpox after they had
contracted cowpox as well
o He inoculated his wife and children with cowpox to avoid smallpox epidemic =
succeeded
• Jesty’s actions constituted the first known real vaccine – the use of cowpox to protect against
smallpox
• Edward Jenner then did large scale vaccinations with cowpox
o Cowpox was not widespread, so it was difficult to find for use as a vaccine
o They tried to transport cowpox infected cattle (but an infection only lasts for so long) à
we needed susceptible cattle as well à very complex
o They started arm-to-arm transmission (people are easier to transport than cattle) =
providing large-scale inoculation
§ They used orphans/children infected/susceptible to cowpox and brought them
all over the world = seen as hero’s!
o Of course this did not came without risk: this arm-to-arm transmission enhances the
spread of other diseases (like syphilis and tuberculosis)
• The rinderpest was a cattle plague (18th century), for this they also tried inoculation à disastrous
results!
• In 1855, they started to standardize calf-derived vaccines
2
,2025-2026 Vaccine Technologies Peter Delputte
VACCINE TIMELINE
• Louis Pasteur (1879)
o Serendipity = finding something, when looking for something else
o He was investigating fowl cholera (Pasteurella multocida)
A (short) history of vaccination
o Until some student accidentally messed up
§ He forgot to renew Louisthe
Pasteur
bacterial(1879)
culture– serendipity…
over the
weekend = cells died
§ He decided to§use a culture
Louis Pasteur infrom
Francethe week before
investigated fowl (aged
P. multocida) cholera (Pasteurella multocida)
§ He infected a chicken with this culture, but the chicken
§ Accidental aged P. multocida was used, and this
did not die (it was
didhealthy)
not kill chickens, but protected against
§ When a new (fresh) culture
infection with was
fresh given to chickens
P. multocida (Serendipity)
• Chicken previously infected with the aged
culture survived = immunity
• Chickens not previously infected died
• Henry Toussaint (1880)
o Anthrax vaccine 27
o He noted that the blood of bovines, died of anthrax, were full of bacteria
§ He filtered the blood: bacteria could pass through the filter
§ He heated the blood (10min at 55°C to the action of diluted phenol)
à Both techniques resulted in an attenuated vaccine
• At the beginning of 20th century, 5 human vaccines were in use
o Jenner’s original smallpox vaccine
o Pasteur’s rabies vaccine
o 3 bacterial vaccines: typhoid, cholera and plague
o Immunization with diphtheria or tetanus antitoxin was an accepted, unofficial practice!
• At the end of 19th century: the end of arm-to-arm lymph inoculation for smallpox vaccination à
replaced by the use of glycerinated calf lymph in 1898
• End of 19th century: introduction of the fundamental concepts of vaccinology
• Beginning 20th century: refinements to these theoretical underpinnings
o Not until the advent of cell culture 50 years later would the field again become so
dramatically fertile
A (short) history of vaccination
o First animals were used to ‘grow’ viruses, then embryonated chicken eggs were used
Vaccine timeline
32
3
, 2025-2026 Vaccine Technologies Peter Delputte
VACCINES IN THE 20TH CENTURY
• Typhoid vaccines
o Typhoid fever is a bacterial disease caused by Salmonella typhi
o Typhoid fever symptoms are similar to those of other common GI illnesses, including
fever, headache, nausea, constipation or diarrhea, loss of appetite and a rose-colored
rash on the body
o Typhoid fever may lead to intestinal bleeding and perforation, and this may lead to severe
intestinal damage
o Richard Pfeiffer, Wilhelm Kolle and Almroth Wright worked independently on killed
typhoid vaccines
§ Wright proposed ass immunization of British troops with this killed typhoid
vaccine
§ Result was catastrophic: 58,000 typhoid cases with 9000 deaths in the British
army
§ A broad-based trial showed overwhelming effectiveness of the vaccine
• Bacterins
o “bacterins” as human vaccines in early 20th century
o Bacterins = killed bacteria (antigens) injected parentally
o Can be combined with immune serum = serobacterins
o Most bacterins were prepared and sold without clinical trials
o Fell into disuses in late 1930s as more stringent licensing requirements were imposed by
the federal government
• Toxoid vaccines
o Early 20the century: chemical inactivation of diphtheria and other bacterial toxins let to
the development of the first toxoids: diphtheria and tetanus
o 1909: toxoids provide long-lasting immunity against diphtheria in guinea pigs
o 1923: diphtheria toxin could be transformed into a toxoid by formalin, used together with
antitoxin à later, diphtheria toxoid was used on its own (no antitoxin) with adding
formalin = still used
• Rabies
o Rabies = very deadly viral disease of animals and humans
o 1880: Pasteur’s experimental method of attenuation tried on a human disease à efforts
to isolate the rabies virus were unsuccessful (virus remained invisible)
o Passage of rabies virus in animals
§ Inoculation of a part of a dog’s brain into another dog’s brain: inoculated dogs
died à no attenuation, virus remained lethal
§ Serial passage through several rabbits à virus with stable virulence
o Developing a vaccine with attenuated virulence
§ Suspending sections of spinal cord from rabbits inside flasks to dry in a
moisture-free atmosphere
§ Virulence gradually declined until finally disappearing
§ Louis Pasteur injected these spinal cord sections into rabid dogs, followed by
challenge with rabies à no rabies J
o The first live human vaccine
4
