Vaccines
Module 5
Lecture 1
- Why use different approaches (a9enuated, mRNA, viral vectored)?
o Different pathogens have different pathways of infecFon and require different
immune responses
o Technology changes and adapts to allow new methods
- What happens aIer vaccinaFon?
o Delivery of anFgens to sFmulate an adapFve immune response
o APCs take up anFgen
o APCs enter lymphaFc system and travel to lymphaFc Fssues
o T cells and B cells interact with anFgen and expand to induce ABs
o Most are admin by injecFon
§ Intradermal, subcutaneous, intramuscular
• Allows for different doses to be given
o Can have oral or nasal admin
- Aim of vaccines =
o Induce a memory response
o Eliminate free virus/bacteria
o Eliminate infected cells
Approaches
1. InacFvated or live a9enuated
2. Structural component: protein, toxoid or polysaccharide
3. GeneFc
4. Vectored
TradiFonal Approach 1: inacFvated & live a9enuated
- Use a weakened live or inacFvated killed pathogen to sFmulate immune response
- InacFvaFon
o Via chemical procedure/formalin
o Pathogenicity is eliminated by anFgenicity is intact
o Eg. Polio (IPV)
§ Grown in monkey cells (3 serotypes) + formalin inacFvaFon
§ Induces anFbody response in blood
o Eg. Flu vaccine
§ Grown in embryonated chicken eggs
o Eg. New cholera vaccine
§ Bivalent whole killed cholera
- Live a9enuated (LAV)
o Viral replicaFon occur
o Can induce mild or inapparent disease
o Eg. Smallpox, OPV, BCG, YFV
o Developed via passage in cell culture à repeat the process of growing the
organism in unfavourable condiFons
, o In cell culture à no difficulFes to survival, so virus loses some non-essenFal
genes to become the smallest replicaFng genome
LAV advantages LAV disadvantages
1-2 doses only because of possibility for Cant give to immunocompromised
replicaFon
Lower cost Need to be refrigerated
Admin via route of natural infecFon GeneFc stability is NB for safety
No needles or adjuvants needed Need strict safety levels during
development
InducFon of both adapFve immunity arms Need to balance a9enuaFon with potency
TradiFonal Approaches 2: Components (protein subunits, toxoids and conjugates)
- Use pathogen parts to sFmulate an immune response
- Usually capsid or membrane or cell wall comp (protein)
- Induce anFbody response
- Subunit vaccines
o Clone gene
o Express in bacteria, yeast or cell line (any in vitro expression system)
o Purify protein
o Use of capsular polysaccharides
§ Poorly immunogenic on their own but interact with B cells to induce a
short lived anFbody response (igM) that is largely T cell independent
§ Good immune response when conjugated to a pathogen’s protein like
a toxoid
Subunit advantages Subunit disadvantages
Recombinant DNA tech – fast producFon Expensive
No pathogen genomes or infecFous Injected
pathogens – only parFcles that cannot
cause disease are used
Poorly immunogenic – require mulFple
boosts when not conjugated
No replicaFon or infecFon – no
inflammaFon, poor acFvaFon of adapFve
responses
Pure protein requires adjuvants to mimic
inflammatory response
, New Approaches 1: GeneFc vaccines (DNA and mRNA)
- Use pathogen’s genes to sFmulate an immune response
- mRNA can immediately be translated in the cytoplasm to sFmulate immune
response
- DNA à plasmids, stable
- RNA à unstable, non-amplifying and self-amplifying replicons
New Approaches 2: Vectored Vaccines
- Use another unrelated virus to deliver pathogen’s genes to cells to sFmulate immune
response
- Vector is usually a9enuated so as to not cause disease
- Eg. Adenovirus, YFV vaccine
- ManipulaFon of pre-exisFng vaccines and their viruses to make new vaccines
- Disadvantage = mount response to vector as well as intended pathogen, therefore
can only get a maximum of 1 or 2 shots otherwise may clear vaccine
- Advantages = very visible to immune system
- Mechanism =
o Vector can contain spike proteins, cell envelope genes
o Is taken up into cells and transcribed and translated
o Spike proteins are then expressed on a host cell
o Can be recognized by immune system
- Can be replicaFon competent or replicaFon defecFve
o ReplicaFon competent à require lower doses
§ Viral vector is mutated (does not cause disease) but can replicate in
body
• Eg. VSV vaccine vector
o For Erbevo (ebola vaccine)
§ Enters cell
§ RNA translated into protein
§ New parFcles can form in cells and affect other
cells to mount a greater immune response
Module 5
Lecture 1
- Why use different approaches (a9enuated, mRNA, viral vectored)?
o Different pathogens have different pathways of infecFon and require different
immune responses
o Technology changes and adapts to allow new methods
- What happens aIer vaccinaFon?
o Delivery of anFgens to sFmulate an adapFve immune response
o APCs take up anFgen
o APCs enter lymphaFc system and travel to lymphaFc Fssues
o T cells and B cells interact with anFgen and expand to induce ABs
o Most are admin by injecFon
§ Intradermal, subcutaneous, intramuscular
• Allows for different doses to be given
o Can have oral or nasal admin
- Aim of vaccines =
o Induce a memory response
o Eliminate free virus/bacteria
o Eliminate infected cells
Approaches
1. InacFvated or live a9enuated
2. Structural component: protein, toxoid or polysaccharide
3. GeneFc
4. Vectored
TradiFonal Approach 1: inacFvated & live a9enuated
- Use a weakened live or inacFvated killed pathogen to sFmulate immune response
- InacFvaFon
o Via chemical procedure/formalin
o Pathogenicity is eliminated by anFgenicity is intact
o Eg. Polio (IPV)
§ Grown in monkey cells (3 serotypes) + formalin inacFvaFon
§ Induces anFbody response in blood
o Eg. Flu vaccine
§ Grown in embryonated chicken eggs
o Eg. New cholera vaccine
§ Bivalent whole killed cholera
- Live a9enuated (LAV)
o Viral replicaFon occur
o Can induce mild or inapparent disease
o Eg. Smallpox, OPV, BCG, YFV
o Developed via passage in cell culture à repeat the process of growing the
organism in unfavourable condiFons
, o In cell culture à no difficulFes to survival, so virus loses some non-essenFal
genes to become the smallest replicaFng genome
LAV advantages LAV disadvantages
1-2 doses only because of possibility for Cant give to immunocompromised
replicaFon
Lower cost Need to be refrigerated
Admin via route of natural infecFon GeneFc stability is NB for safety
No needles or adjuvants needed Need strict safety levels during
development
InducFon of both adapFve immunity arms Need to balance a9enuaFon with potency
TradiFonal Approaches 2: Components (protein subunits, toxoids and conjugates)
- Use pathogen parts to sFmulate an immune response
- Usually capsid or membrane or cell wall comp (protein)
- Induce anFbody response
- Subunit vaccines
o Clone gene
o Express in bacteria, yeast or cell line (any in vitro expression system)
o Purify protein
o Use of capsular polysaccharides
§ Poorly immunogenic on their own but interact with B cells to induce a
short lived anFbody response (igM) that is largely T cell independent
§ Good immune response when conjugated to a pathogen’s protein like
a toxoid
Subunit advantages Subunit disadvantages
Recombinant DNA tech – fast producFon Expensive
No pathogen genomes or infecFous Injected
pathogens – only parFcles that cannot
cause disease are used
Poorly immunogenic – require mulFple
boosts when not conjugated
No replicaFon or infecFon – no
inflammaFon, poor acFvaFon of adapFve
responses
Pure protein requires adjuvants to mimic
inflammatory response
, New Approaches 1: GeneFc vaccines (DNA and mRNA)
- Use pathogen’s genes to sFmulate an immune response
- mRNA can immediately be translated in the cytoplasm to sFmulate immune
response
- DNA à plasmids, stable
- RNA à unstable, non-amplifying and self-amplifying replicons
New Approaches 2: Vectored Vaccines
- Use another unrelated virus to deliver pathogen’s genes to cells to sFmulate immune
response
- Vector is usually a9enuated so as to not cause disease
- Eg. Adenovirus, YFV vaccine
- ManipulaFon of pre-exisFng vaccines and their viruses to make new vaccines
- Disadvantage = mount response to vector as well as intended pathogen, therefore
can only get a maximum of 1 or 2 shots otherwise may clear vaccine
- Advantages = very visible to immune system
- Mechanism =
o Vector can contain spike proteins, cell envelope genes
o Is taken up into cells and transcribed and translated
o Spike proteins are then expressed on a host cell
o Can be recognized by immune system
- Can be replicaFon competent or replicaFon defecFve
o ReplicaFon competent à require lower doses
§ Viral vector is mutated (does not cause disease) but can replicate in
body
• Eg. VSV vaccine vector
o For Erbevo (ebola vaccine)
§ Enters cell
§ RNA translated into protein
§ New parFcles can form in cells and affect other
cells to mount a greater immune response
