Module 5: Vaccinology and Cancer Immunotherapy
Prevention of infectious diseases
Active immunization: the induction of immunity in a body following exposure to antigens (natural or
artificial) leads to B and T cell responses and provides immunological memory
Passive immunity: can be gained by transfer of serum or gamma globulin from an immunized donor
to a non-immune individual. Short-lived and no immunological memory is built up
Antibody-based therapies: the use of antibodies against a variety of diseases
Herd immunity
If most people are immunized, then the spread of a disease is contained
Handy for people that can not be vaccinated due to allergies
What is a vaccine?
Artificial active immunization
Consists of a (modified) antigen
o inactivated or weakened pathogen, an immunogenic part of pathogen or derived
from a toxin
Induces memory
The development of vaccination
Smallpox:
Caused by either the virus Variola major or Variola minor
Direct transmission from human to human
The principle of attenuation
Attenuation: the process by which a pathogen is made less virulent or harmless in a laboratory
setting so it can be used for vaccinations
Development of the tuberculosis vaccine
Serial passage: an infectious pathogen is used to infect an animal cell line, replicate and harvested
over and over, mutating the pathogen until an attenuated strain is obtained that would cause
immunity
Nowadays it’s possible to determine the genome sequence of any pathogen making it
possible to design live attenuated pathogen strains
Classical vaccines: Live attenuated vaccines
The major advantage of using live attenuated vaccines is that the pathogen can still multiply in the
vaccinated individual in a way that closely resembles an actual infection
Stimulating a cell-mediated immunity
Continuous stimulation of the immune system
Disadvantage: virus can revert to its virulent state, not suitable for weak person
Inactivated vaccines
Consists of a fully inactivated pathogen
Pathogen can no longer replicate, while the structure of the pathogen remains intact
o Making it impossible to return to viral state
Results in a less strong immune response
Mainly induces B cell and T helper responses and no cytotoxic T cells
o Less effective
o Multiple boosters needed
1
, Bacterial vaccines based on toxins or polysaccharides
Toxins are often the cause of disease in bacterial infections
Toxoid: harmless version of the toxin as vaccine
Do not give lifelong immunity, require boosters
Conjugate vaccines: works against the polysaccharides found on the capsule of gram negative and
gram positive bacteria
polysaccharides are coupled to an immunogenic protein to allow not only polysaccharide
specific B-cells, but also T helper cell activation via the protein module
Defining factors of a good vaccine: Considerations for making a vaccine
Efficacy: the ability to raise a protective immune response
booster vaccinations: follows initial immunization if that didn’t reach a sufficient level of protection
The working mechanism of the vaccine should correlate with that of the pathogen to ensure optimal
immunogenicity
Considerations:
The place of entry, which is correlated with the type of immunoglobulin needed
Whether the pathogen is intracellular or extracellular
Which type of immune response is primed normally
Whether herd immunity is a factor to take into consideration
Which part of the pathogen is needed to induce neutralizing immunity
o Neutralizing epitopes: the part of an antigen (for a protein the part of the amino acid
sequence) to which antibodies (or T-cells) should bind in order to neutralize the
pathogen, these are most often surface components
Antigenic variability like antigenic drift and shift
If the immune system is effect by the pathogen
Safety aspects
Safety standards:
limited or none side effects
no allergic reactions
low risks when vaccinating immune-compromised individuals
Live-attenuated pathogens have an inherent risk of contamination, while inactivated vaccines have a
risk of improper inactivation. Another risk is loss of immunogenicity (the potency to induce an
immune response)
Maternal antibodies and vaccines
Maternal antibodies are transferred to the fetus during pregnancy (IgG),
via egg yolk in birds (IgY) or to the new-borne child during breast feeding
(IgA) passive immunization
Critical susceptible period: the time frame when the levels of maternal
antibodies are too low for absolute protection against a pathogen, but are
sufficient to inactivate the (attenuated) vaccine
Vaccines by design: Subunit vaccines
Subunit vaccines: composed of immunogenic components of a pathogen that cause a strong immune
response and lead to neutralizing immunity
Commonly consist of proteins (or part thereof) or polysaccharides
Safest vaccines
2
Prevention of infectious diseases
Active immunization: the induction of immunity in a body following exposure to antigens (natural or
artificial) leads to B and T cell responses and provides immunological memory
Passive immunity: can be gained by transfer of serum or gamma globulin from an immunized donor
to a non-immune individual. Short-lived and no immunological memory is built up
Antibody-based therapies: the use of antibodies against a variety of diseases
Herd immunity
If most people are immunized, then the spread of a disease is contained
Handy for people that can not be vaccinated due to allergies
What is a vaccine?
Artificial active immunization
Consists of a (modified) antigen
o inactivated or weakened pathogen, an immunogenic part of pathogen or derived
from a toxin
Induces memory
The development of vaccination
Smallpox:
Caused by either the virus Variola major or Variola minor
Direct transmission from human to human
The principle of attenuation
Attenuation: the process by which a pathogen is made less virulent or harmless in a laboratory
setting so it can be used for vaccinations
Development of the tuberculosis vaccine
Serial passage: an infectious pathogen is used to infect an animal cell line, replicate and harvested
over and over, mutating the pathogen until an attenuated strain is obtained that would cause
immunity
Nowadays it’s possible to determine the genome sequence of any pathogen making it
possible to design live attenuated pathogen strains
Classical vaccines: Live attenuated vaccines
The major advantage of using live attenuated vaccines is that the pathogen can still multiply in the
vaccinated individual in a way that closely resembles an actual infection
Stimulating a cell-mediated immunity
Continuous stimulation of the immune system
Disadvantage: virus can revert to its virulent state, not suitable for weak person
Inactivated vaccines
Consists of a fully inactivated pathogen
Pathogen can no longer replicate, while the structure of the pathogen remains intact
o Making it impossible to return to viral state
Results in a less strong immune response
Mainly induces B cell and T helper responses and no cytotoxic T cells
o Less effective
o Multiple boosters needed
1
, Bacterial vaccines based on toxins or polysaccharides
Toxins are often the cause of disease in bacterial infections
Toxoid: harmless version of the toxin as vaccine
Do not give lifelong immunity, require boosters
Conjugate vaccines: works against the polysaccharides found on the capsule of gram negative and
gram positive bacteria
polysaccharides are coupled to an immunogenic protein to allow not only polysaccharide
specific B-cells, but also T helper cell activation via the protein module
Defining factors of a good vaccine: Considerations for making a vaccine
Efficacy: the ability to raise a protective immune response
booster vaccinations: follows initial immunization if that didn’t reach a sufficient level of protection
The working mechanism of the vaccine should correlate with that of the pathogen to ensure optimal
immunogenicity
Considerations:
The place of entry, which is correlated with the type of immunoglobulin needed
Whether the pathogen is intracellular or extracellular
Which type of immune response is primed normally
Whether herd immunity is a factor to take into consideration
Which part of the pathogen is needed to induce neutralizing immunity
o Neutralizing epitopes: the part of an antigen (for a protein the part of the amino acid
sequence) to which antibodies (or T-cells) should bind in order to neutralize the
pathogen, these are most often surface components
Antigenic variability like antigenic drift and shift
If the immune system is effect by the pathogen
Safety aspects
Safety standards:
limited or none side effects
no allergic reactions
low risks when vaccinating immune-compromised individuals
Live-attenuated pathogens have an inherent risk of contamination, while inactivated vaccines have a
risk of improper inactivation. Another risk is loss of immunogenicity (the potency to induce an
immune response)
Maternal antibodies and vaccines
Maternal antibodies are transferred to the fetus during pregnancy (IgG),
via egg yolk in birds (IgY) or to the new-borne child during breast feeding
(IgA) passive immunization
Critical susceptible period: the time frame when the levels of maternal
antibodies are too low for absolute protection against a pathogen, but are
sufficient to inactivate the (attenuated) vaccine
Vaccines by design: Subunit vaccines
Subunit vaccines: composed of immunogenic components of a pathogen that cause a strong immune
response and lead to neutralizing immunity
Commonly consist of proteins (or part thereof) or polysaccharides
Safest vaccines
2
