Vaccines Flashcards
Immunisation is an … process by which an individual is rendered …
Immunisation is an artificial process by which an individual is rendered immune
What is Immunisation?
Immunisation is an artificial process by which an individual is rendered immune
… immunisation – no immune response in recipient
Passive immunisation – no immune response in recipient
… immunisation (…) – recipient develops a protective adaptive immune response
Active immunisation (vaccination) – recipient develops a protective adaptive immune response
Passive vs Active Immunisation
- Passive immunisation – no immune response in recipient
- Active immunisation (vaccination) – recipient develops a protective adaptive immune response
Immunisation is one of the cheapest and most effective methods of improving … and reducing …
Immunisation is one of the cheapest and most effective methods of improving survival and reducing morbidity
Immunisation estimated reduction in mortality worldwide … million/ yr
Immunisation estimated reduction in mortality worldwide 3 million/ yr
Variola = … virus
Variola =smallpox virus

Variolation
- Variola = … virus
- For variolation, fluid harvested from pustules of … individuals and injected under skin of recipient
- Crude method of obtaining an ‘…’ vaccine
- Documented practice in Far East, Middle East and South Asia from 1000AD
- Limited use in UK (1700s)
- Variola =smallpox virus
- For variolation, fluid harvested from pustules of recovering individuals and injected under skin of recipient
- Crude method of obtaining an ‘inactivated’ vaccine
- Documented practice in Far East, Middle East and South Asia from 1000AD
- Limited use in UK (1700s)
Jenner
- Used fluid from … lesions to protect against … infection in 1796; recipient was James Phipps, aged 8
- Subsequently experimented with several other children, including his own infant son; published findings in 1798
- The first documented use of a live-attenuated vaccine and the birth of modern immunisation
- Used fluid from cowpox lesions to protect against smallpox infection in 1796; recipient was James Phipps, aged 8
- Subsequently experimented with several other children, including his own infant son; published findings in 1798
- The first documented use of a live-attenuated vaccine and the birth of modern immunisation
- Jenner used fluid from cowpox lesions to protect against … infection in 1796; recipient was James Phipps, aged 8
- Subsequently experimented with several other children, including his own infant son; published findings in 1798
- The first documented use of a …-attenuated vaccine and the birth of … immunisation
- Jenner used fluid from cowpox lesions to protect against … infection in 1796; recipient was James Phipps, aged 8
- Subsequently experimented with several other children, including his own infant son; published findings in 1798
- The first documented use of a live-attenuated vaccine and the birth of modern immunisation
Passive immunisation
- Immunity conferred without an … host response on behalf of recipient
- Passive vaccines are preparations of … taken from hyper-immune donors, either human or animal
- Examples:
- Immunoglobulin replacement in antibody deficiency
- VZV prophylaxis eg during exposure during …
- Anti-toxin therapies eg … anti-serum
- Protection is temporary
- Immunity conferred without an active host response on behalf of recipient
- Passive vaccines are preparations of antibodies taken from hyper-immune donors, either human or animal
- Examples:
- Immunoglobulin replacement in antibody deficiency
- VZV prophylaxis eg during exposure during pregnancy
- Anti-toxin therapies eg snake anti-serum
- Protection is temporary
Passive immunisation
- Immunity conferred without an active host response on behalf of recipient
- Passive vaccines are preparations of antibodies taken from …-immune donors, either human or animal
- Examples:
- Immunoglobulin replacement in antibody deficiency
- VZV prophylaxis eg during exposure during pregnancy
- Anti-toxin therapies eg snake anti-serum
- Protection is …
- Immunity conferred without an active host response on behalf of recipient
- Passive vaccines are preparations of antibodies taken from hyper-immune donors, either human or animal
- Examples:
- Immunoglobulin replacement in antibody deficiency
- VZV prophylaxis eg during exposure during pregnancy
- Anti-toxin therapies eg snake anti-serum
- Protection is temporary
Is passive immunisation protection permanent or temporary?
temporary
VZV exposure during pregnancy
- VZV causes …
- If they have had …, no need to do anything
- If no history or unsure - blood test to check for VZV IgG - if positive, reassure (has memory response - immune to …) If negative or equivocal, give VZV immunoglobulin to protect against infection
- VZV during pregnancy can cause fetal complications.
- In case of exposure, women should contact their GP, Midwife or Virology Dept. Urgent VZV serology is available when required
- VZV causes chickenpox
- If they have had chickenpox, no need to do anything
- If no history or unsure - blood test to check for VZV IgG - if positive, reassure (has memory response - immune to chickenpox) If negative or equivocal, give VZV immunoglobulin to protect against infection
- VZV during pregnancy can cause fetal complications.
- In case of exposure, women should contact their GP, Midwife or Virology Dept. Urgent VZV serology is available when required

VZV exposure during pregnancy
- VZV causes chickenpox
- If they have had chickenpox, no need to do anything
- If no history or unsure - blood test to check for VZV IgG - if …, reassure (has memory response - immune to chickenpox) If … or …, give VZV immunoglobulin to protect against infection
- VZV during pregnancy can cause fetal complications.
- In case of exposure, women should contact their GP, Midwife or Virology Dept. Urgent VZV serology is available when required
- VZV causes chickenpox
- If they have had chickenpox, no need to do anything
- If no history or unsure - blood test to check for VZV IgG - if positive, reassure (has memory response - immune to chickenpox) If negative or equivocal, give VZV immunoglobulin to protect against infection
- VZV during pregnancy can cause fetal complications.
- In case of exposure, women should contact their GP, Midwife or Virology Dept. Urgent VZV serology is available when required

VZV exposure during pregnancy
- VZV causes chickenpox
- If they have had chickenpox, no need to do anything
- If no history or unsure - blood test to check for VZV IgG - if positive, reassure (has memory response - immune to chickenpox) If negative or equivocal, give VZV immunoglobulin to protect against infection
- VZV during pregnancy can cause … …
- In case of exposure, women should contact their GP, Midwife or Virology Dept. Urgent VZV serology is available when required
- VZV causes chickenpox
- If they have had chickenpox, no need to do anything
- If no history or unsure - blood test to check for VZV IgG - if positive, reassure (has memory response - immune to chickenpox) If negative or equivocal, give VZV immunoglobulin to protect against infection
- VZV during pregnancy can cause fetal complications.
- In case of exposure, women should contact their GP, Midwife or Virology Dept. Urgent VZV serology is available when required

VZV exposure during pregnancy
- VZV causes chickenpox
- If they have had chickenpox, what is done?
- If no history or unsure - blood test to check for VZV … - if positive, reassure (has memory response - immune to chickenpox) If negative or equivocal, give VZV immunoglobulin to protect against infection
- VZV during pregnancy can cause fetal complications.
- In case of exposure, women should contact their GP, Midwife or Virology Dept. Urgent VZV serology is available when required
- VZV causes chickenpox
- If they have had chickenpox, no need to do anything
- If no history or unsure - blood test to check for VZV IgG - if positive, reassure (has memory response - immune to chickenpox) If negative or equivocal, give VZV immunoglobulin to protect against infection
- VZV during pregnancy can cause fetal complications.
- In case of exposure, women should contact their GP, Midwife or Virology Dept. Urgent VZV serology is available when required

In pregnant women with no history of chickenpox or unsure, do bloods to check for VZV IgG - If positive, what does that mean?
Reassure - they are immune, if negative this means they have not had chickenpox before and give VZV immunoglobulin
Active immunisation (vaccination)
- Immunity conferred in recipient following the generation of an … immune response
- General principle is to stimulate an … immune response without causing …-… infection
- Immunity conferred in recipient following the generation of an adaptive immune response
- General principle is to stimulate an adaptive immune response without causing clinically-apparent infection

Active immunisation is the same as …
Active immunisation (vaccination)
General principles of Vaccination (1)
- To be effective, vaccines need to be administered to targeted … in advance of … to the pathogen of interest
- Vaccination of sufficient numbers impacts the transmission dynamic so that even unimmunised individuals are at … risk – called … …
- As vaccines are given to … individuals, the risk-to-benefit ratio requires that vaccines meet high safety standards
- To be effective, vaccines need to be administered to targeted cohorts in advance of exposure to the pathogen of interest
- Vaccination of sufficient numbers impacts the transmission dynamic so that even unimmunised individuals are at low risk – called herd immunity
- As vaccines are given to healthy individuals, the risk-to-benefit ratio requires that vaccines meet high safety standards
General principles of Vaccination (2)
- Most vaccines work by generating a long-lasting, high-affinity I… antibody response
- These antibodies are sufficient to prevent primary infection
- A strong … T cell response is a pre-requisite for this
- The most effective vaccines are for diseases where natural exposure results in protective immunity
- ‘Problem’ diseases are generally those where the immune system cannot eliminate infection or generate …-… protective immunity during natural infection
- Eg MTB, HIV, malaria
- Most vaccines work by generating a long-lasting, high-affinity IgG antibody response
- These antibodies are sufficient to prevent primary infection
- A strong CD4 T cell response is a pre-requisite for this
- The most effective vaccines are for diseases where natural exposure results in protective immunity
- ‘Problem’ diseases are generally those where the immune system cannot eliminate infection or generate long-lasting protective immunity during natural infection
- Eg MTB, HIV, malaria
General principles of Vaccination (2)
- Most vaccines work by generating a long-lasting, …-affinity IgG antibody response
- These antibodies are sufficient to prevent … infection
- A strong CD4 T cell response is a pre-requisite for this
- The most effective vaccines are for diseases where natural exposure results in protective immunity
- ‘…’ diseases are generally those where the immune system cannot eliminate infection or generate long-lasting protective immunity during natural infection
- Eg MTB, HIV, malaria
- Most vaccines work by generating a long-lasting, high-affinity IgG antibody response
- These antibodies are sufficient to prevent primary infection
- A strong CD4 T cell response is a pre-requisite for this
- The most effective vaccines are for diseases where natural exposure results in protective immunity
- ‘Problem’ diseases are generally those where the immune system cannot eliminate infection or generate long-lasting protective immunity during natural infection
- Eg MTB, HIV, malaria
What goes into a vaccine?
- …
- To stimulate an …-specific T and B cell response
- …
- Immune potentiators to increase the immunogenicity of the vaccine
- ‘Excipients’
- Various diluents and additives required for vaccine integrity
-
Antigen
- To stimulate an antigen-specific T and B cell response
-
Adjuvants
- Immune potentiators to increase the immunogenicity of the vaccine
- ‘Excipients’
- Various diluents and additives required for vaccine integrity
What goes into a vaccine?
- Antigen
- To … an antigen-specific T and B cell response
- Adjuvants
- Immune potentiators to increase the immunogenicity of the vaccine
- ‘…’
- Various diluents and additives required for vaccine integrity
- Antigen
- To stimulate an antigen-specific T and B cell response
- Adjuvants
- Immune potentiators to increase the immunogenicity of the vaccine
- ‘Excipients’
- Various diluents and additives required for vaccine integrity
Classification of active vaccines on the basis of the antigen
- Active Vaccines - divided into … organism or subunit
- … organism
- Live-attenuated vaccine
- Inactivated (killed)
- S..
- Toxoids
- Capsular polysaccharide
- Conjugated polysaccharide
- Recombinant subunit
- ?mRNA, VLPs, viral vector
- Active Vaccines - divided into whole organism or subunit
-
Whole organism
- Live-attenuated vaccine
- Inactivated (killed)
-
Subunit
- Toxoids
- Capsular polysaccharide
- Conjugated polysaccharide
- Recombinant subunit
- ?mRNA, VLPs, viral vector

Classification of active vaccines on the basis of the antigen
- Active Vaccines - divided into whole organism or subunit
- Whole organism
- …-… vaccine
- Inactivated (killed)
- Subunit
- T…
- Capsular polysaccharide
- Conjugated polysaccharide
- Recombinant subunit
- ?mRNA, VLPs, viral vector
- Active Vaccines - divided into whole organism or subunit
- Whole organism
- Live-attenuated vaccine
- Inactivated (killed)
- Subunit
- Toxoids
- Capsular polysaccharide
- Conjugated polysaccharide
- Recombinant subunit
- ?mRNA, VLPs, viral vector

Classification of active vaccines on the basis of the antigen
- Active Vaccines - divided into whole organism or subunit
- Whole organism
- Live-attenuated vaccine
- … (killed)
- Subunit
- Toxoids
- C.. polysaccharide
- C… polysaccharide
- Recombinant subunit
- ?mRNA, VLPs, viral vector
- Active Vaccines - divided into whole organism or subunit
- Whole organism
- Live-attenuated vaccine
- Inactivated (killed)
- Subunit
- Toxoids
- Capsular polysaccharide
- Conjugated polysaccharide
- Recombinant subunit
- ?mRNA, VLPs, viral vector

Classification of active vaccines on the basis of the antigen
- Active Vaccines - divided into whole organism or subunit
- Whole organism
- Live-attenuated vaccine
- Inactivated (killed)
- Subunit
- Toxoids
- Capsular polysaccharide
- Conjugated polysaccharide
- … subunit
- ?..RNA, VLPs, viral …
- Active Vaccines - divided into whole organism or subunit
- Whole organism
- Live-attenuated vaccine
- Inactivated (killed)
- Subunit
- Toxoids
- Capsular polysaccharide
- Conjugated polysaccharide
- Recombinant subunit
- ?mRNA, VLPs, viral vector

Live-attenuated vaccines
- Live but attenuated organisms used
- Prolonged culture … vivo in non-… conditions
- This selects variants that are adapted to live in …
- These variants are viable in vivo but are no longer able to cause disease
- Live but attenuated organisms used
- Prolonged culture ex vivo in non-physiological conditions
- This selects variants that are adapted to live in culture
- These variants are viable in vivo but are no longer able to cause disease
Live-attenuated vaccines
- Live but attenuated organisms used
- Prolonged culture ex vivo in non-physiological conditions
- This selects variants that are adapted to live in culture
- These variants are viable … vivo but are no longer able to cause …
- Live but attenuated organisms used
- Prolonged culture ex vivo in non-physiological conditions
- This selects variants that are adapted to live in culture
- These variants are viable in vivo but are no longer able to cause disease
Examples of Live-attenuated vaccines
- M…
- M…
- R…
- P… (Sabin)
- B…
- Cholera
- Zoster
- VZV (not routinely used for primary prevention in UK at present)
- Live influenza (not main product in UK at present)
- Measles
- Mumps
- Rubella
- Polio (Sabin)
- BCG
- Cholera
- Zoster
- VZV (not routinely used for primary prevention in UK at present)
- Live influenza (not main product in UK at present)
Pros and cons of live vaccines
- Replication … …, therefore produces highly effective and durable responses
- In case of viral vaccine, intracellular infection leads to good … response
- Repeated … not required
- In some diseases, may get secondary protection of unvaccinated individuals, who are infected with the live-attenuated vaccine strain eg polio
- Storage problems, short shelf-life
- May revert to wild type Eg vaccine associated poliomyelitis: around 1 in 750 000 recipients
- Immunocompromised recipients may develop clinical disease
- Replication within host, therefore produces highly effective and durable responses
- In case of viral vaccine, intracellular infection leads to good CD8 response
- Repeated boosting not required
- In some diseases, may get secondary protection of unvaccinated individuals, who are infected with the live-attenuated vaccine strain eg polio
- Storage problems, short shelf-life
- May revert to wild type Eg vaccine associated poliomyelitis: around 1 in 750 000 recipients
- Immunocompromised recipients may develop clinical disease
Pros and cons of live vaccines
- Replication within host, therefore produces highly effective and durable responses
- In case of viral vaccine, intracellular infection leads to good CD8 response
- Repeated boosting not required
- In some diseases, may get … protection of … individuals, who are infected with the live-attenuated vaccine strain eg polio
- … problems, short …-life
- May revert to wild type Eg vaccine associated poliomyelitis: around 1 in 750 000 recipients
- Immunocompromised recipients may develop clinical disease
- Replication within host, therefore produces highly effective and durable responses
- In case of viral vaccine, intracellular infection leads to good CD8 response
- Repeated boosting not required
- In some diseases, may get secondary protection of unvaccinated individuals, who are infected with the live-attenuated vaccine strain eg polio
- Storage problems, short shelf-life
- May revert to wild type Eg vaccine associated poliomyelitis: around 1 in 750 000 recipients
- Immunocompromised recipients may develop clinical disease
Pros and cons of live vaccines
- Replication within host, therefore produces highly effective and durable responses
- In case of viral vaccine, intracellular infection leads to good CD8 response
- Repeated boosting not required
- In some diseases, may get secondary protection of unvaccinated individuals, who are infected with the live-attenuated vaccine strain eg polio
- Storage problems, short shelf-life
- May revert to … type Eg vaccine associated poliomyelitis: around 1 in 750 000 recipients
- … recipients may develop clinical disease
- Replication within host, therefore produces highly effective and durable responses
- In case of viral vaccine, intracellular infection leads to good CD8 response
- Repeated boosting not required
- In some diseases, may get secondary protection of unvaccinated individuals, who are infected with the live-attenuated vaccine strain eg polio
- Storage problems, short shelf-life
- May revert to wild type Eg vaccine associated poliomyelitis: around 1 in 750 000 recipients
- Immunocompromised recipients may develop clinical disease
Varicella-Zoster Vaccine
- Primary infection = …
- Cellular and humoral immunity provide lifelong protection, but viruses establishes permanent infection of sensory ganglia
- Viral reactivation= …
- Particularly elderly, fairly debilitating and may cause long-term neuropathic pain
- Primary infection = chickenpox
- Cellular and humoral immunity provide lifelong protection, but viruses establishes permanent infection of sensory ganglia
- Viral reactivation= zoster (shingles)
- Particularly elderly, fairly debilitating and may cause long-term neuropathic pain

Varicella-Zoster Vaccine
- Primary infection = chickenpox
- Cellular and humoral immunity provide … protection, but viruses establishes … infection of sensory ganglia
- Viral … = zoster (shingles)
- Particularly elderly, fairly debilitating and may cause long-term neuropathic pain
- Primary infection = chickenpox
- Cellular and humoral immunity provide lifelong protection, but viruses establishes permanent infection of sensory ganglia
- Viral reactivation=zoster (shingles)
- Particularly elderly, fairly debilitating and may cause long-term neuropathic pain

Varicella-Zoster Vaccine
- Primary infection = …
- Cellular and humoral immunity provide lifelong protection, but viruses establishes permanent infection of sensory ganglia
- Viral reactivation= Zoster (shingles)
- Particularly …, fairly … and may cause long-term … pain
- Primary infection = chickenpox
- Cellular and humoral immunity provide lifelong protection, but viruses establishes permanent infection of sensory ganglia
- Viral reactivation= zoster (shingles)
- Particularly elderly, fairly debilitating and may cause long-term neuropathic pain

Varicella-Zoster Vaccine
- …-… VZV, works by induction of anti-VZV antibodies
- …% effective at preventing chickenpox
- Attenuated virus does establish infection of sensory ganglia, but subsequent zoster is probably rare
- ..-..% mild post-vaccination varicella infection
- Not on UK schedule at present, because:
- VZV is a fairly benign childhood infection
- ?Schedule is already crowded and controversial
- Safety concerns based on evidence from other countries
- ‘Disease shift’ to unvaccinated adults, in whom VZV is less well tolerated
- Increase in zoster – probably reduced immune boosting in adults
- Live-attenuated VZV, works by induction of anti-VZV antibodies
- 95% effective at preventing chickenpox
- Attenuated virus does establish infection of sensory ganglia, but subsequent zoster is probably rare
- 3-5% mild post-vaccination varicella infection
- Not on UK schedule at present, because:
- VZV is a fairly benign childhood infection
- ?Schedule is already crowded and controversial
- Safety concerns based on evidence from other countries
- ‘Disease shift’ to unvaccinated adults, in whom VZV is less well tolerated
- Increase in zoster – probably reduced immune boosting in adults
Varicella-Zoster Vaccine
- Live-attenuated VZV, works by induction of anti-VZV antibodies
- 95% effective at preventing chickenpox
- Attenuated virus does establish infection of sensory …, but subsequent zoster is probably rare
- 3-5% mild post-vaccination varicella infection
- Not on UK schedule at present, because:
- VZV is a fairly … childhood infection
- ?Schedule is already crowded and c…
- … concerns based on evidence from other countries
- ‘Disease shift’ to unvaccinated adults, in whom VZV is less well tolerated
- Increase in zoster – probably reduced immune boosting in adults
- Live-attenuated VZV, works by induction of anti-VZV antibodies
- 95% effective at preventing chickenpox
- Attenuated virus does establish infection of sensory ganglia, but subsequent zoster is probably rare
- 3-5% mild post-vaccination varicella infection
- Not on UK schedule at present, because:
- VZV is a fairly benign childhood infection
- ?Schedule is already crowded and controversial
-
Safety concerns based on evidence from other countries
- ‘Disease shift’ to unvaccinated adults, in whom VZV is less well tolerated
- Increase in zoster – probably reduced immune boosting in adults
Varicella-Zoster Vaccine
- Live-attenuated VZV, works by induction of anti-VZV antibodies
- 95% effective at preventing chickenpox
- Attenuated virus does establish infection of sensory ganglia, but subsequent zoster is probably rare
- 3-5% mild post-vaccination varicella infection
- Not on UK schedule at present, because:
- VZV is a fairly benign childhood infection
- ?Schedule is already crowded and controversial
- Safety concerns based on evidence from other countries
- ‘… shift’ to unvaccinated adults, in whom VZV is less well tolerated
- Increase in … – probably reduced immune boosting in adults
- Live-attenuated VZV, works by induction of anti-VZV antibodies
- 95% effective at preventing chickenpox
- Attenuated virus does establish infection of sensory ganglia, but subsequent zoster is probably rare
- 3-5% mild post-vaccination varicella infection
- Not on UK schedule at present, because:
- VZV is a fairly benign childhood infection
- ?Schedule is already crowded and controversial
- Safety concerns based on evidence from other countries
- ‘Disease shift’ to unvaccinated adults, in whom VZV is less well tolerated
- Increase in zoster – probably reduced immune boosting in adults
The varicella-zoster vaccine is …% effective at preventing chickenpox
95% effective at preventing chickenpox
Is VZV (Varicella-Zoster vaccine) on UK vaccination schedule?
- Not on UK schedule at present, because:
- VZV is a fairly benign childhood infection
- ?Schedule is already crowded and controversial
- Safety concerns based on evidence from other countries
- ‘Disease shift’ to unvaccinated adults, in whom VZV is less well tolerated
- Increase in zoster – probably reduced immune boosting in adults
Zoster, immunity and aging
- The incidence of zoster … with age, in parallel with … cell-mediated immune responses to zoster
- The incidence of zoster increases with age, in parallel with declining cell-mediated immune responses to zoster

Zoster vaccination
- Similar VZV preparation to that used for … disease, but much … dose
- Aims to boost memory T cell responses to VZV
- In over 60s, 50% reduction in zoster incidence after vaccination compared to controls; reduced severity and complications amongst vaccinated cases
- Similar VZV preparation to that used for primary disease, but much higher dose
- Aims to boost memory T cell responses to VZV
- In over 60s, 50% reduction in zoster incidence after vaccination compared to controls; reduced severity and complications amongst vaccinated cases

Zoster vaccination
- Similar VZV preparation to that used for primary disease, but much … dose
- Aims to boost … T cell responses to VZV
- In over 60s, 50% reduction in zoster incidence after vaccination compared to controls; reduced severity and complications amongst vaccinated cases
- Similar VZV preparation to that used for primary disease, but much higher dose
- Aims to boost memory T cell responses to VZV
- In over 60s, 50% reduction in zoster incidence after vaccination compared to controls; reduced severity and complications amongst vaccinated cases

Zoster vaccination
- Similar VZV preparation to that used for … disease, but much … dose
- Aims to boost memory T cell responses to VZV
- In over 60s, …% reduction in zoster incidence after vaccination compared to controls; reduced severity and complications amongst vaccinated cases
- Similar VZV preparation to that used for primary disease, but much higher dose
- Aims to boost memory T cell responses to VZV
- In over 60s, 50% reduction in zoster incidence after vaccination compared to controls; reduced severity and complications amongst vaccinated cases

Zoster vaccination
- Similar VZV preparation to that used for primary disease, but much … dose
- Aims to boost memory T cell responses to VZV
- In over 60s, 50% reduction in zoster incidence after vaccination compared to controls; reduced … and … amongst vaccinated cases
- Similar VZV preparation to that used for primary disease, but much higher dose
- Aims to boost memory T cell responses to VZV
- In over 60s, 50% reduction in zoster incidence after vaccination compared to controls; reduced severity and complications amongst vaccinated cases

Poliomyelitis
- …virus establishes infection in … and GI tract (alimentary phase)
- Spreads to peyers patches then disseminated via lymphatics
- Haematogenous spread (viremia phase)
- …% of patients develop neurological phase: replication in motor neurones in spinal cord, brainstem and motor cortex, leading to denervation and flaccid paralysis
- Enterovirus establishes infection in oropharynx and GI tract (alimentary phase)
- Spreads to peyers patches then disseminated via lymphatics
- Haematogenous spread (viremia phase)
- 1% of patients develop neurological phase: replication in motor neurones in spinal cord, brainstem and motor cortex, leading to denervation and flaccid paralysis
Poliomyelitis
- Enterovirus establishes infection in oropharynx and … tract (… phase)
- Spreads to peyers patches then disseminated via lymphatics
- Haematogenous spread (viremia phase)
- 1% of patients develop … phase: replication in motor neurones in spinal cord, brainstem and motor cortex, leading to denervation and flaccid paralysis
- Enterovirus establishes infection in oropharynx and GI tract (alimentary phase)
- Spreads to peyers patches then disseminated via lymphatics
- Haematogenous spread (viremia phase)
- 1% of patients develop neurological phase: replication in motor neurones in spinal cord, brainstem and motor cortex, leading to denervation and flaccid paralysis
Poliomyelitis
- Enterovirus establishes infection in oropharynx and GI tract (alimentary phase)
- Spreads to peyers patches then disseminated via lymphatics
- Haematogenous spread (… phase)
- 1% of patients develop neurological phase: replication in motor neurones in spinal cord, brainstem and motor cortex, leading to denervation and flaccid …
- Enterovirus establishes infection in oropharynx and GI tract (alimentary phase)
- Spreads to peyers patches then disseminated via lymphatics
- Haematogenous spread (viremia phase)
- 1% of patients develop neurological phase: replication in motor neurones in spinal cord, brainstem and motor cortex, leading to denervation and flaccid paralysis
Poliomyelitis
- Enterovirus establishes infection in oropharynx and GI tract (alimentary phase)
- Spreads to … patches then disseminated via lymphatics
- … spread (viremia phase)
- 1% of patients develop neurological phase: replication in motor neurones in spinal cord, brainstem and motor cortex, leading to denervation and flaccid paralysis
- Enterovirus establishes infection in oropharynx and GI tract (alimentary phase)
- Spreads to peyers patches then disseminated via lymphatics
- Haematogenous spread (viremia phase)
- 1% of patients develop neurological phase: replication in motor neurones in spinal cord, brainstem and motor cortex, leading to denervation and flaccid paralysis
Salk vs Sabin Polio - Vaccines
- Sabin oral polio vaccine (OPV) = …-…
- Viable virus can be recovered from stool after immunisation
- Highly effective, and also establishes some protection in non-immunised population
- 1 in 750 000 vaccine-associated paralytic polio
- Salk injected polio vaccine (IPV) = …
- Effective, but herd immunity inferior
- OPV better suited to endemic areas, where benefits of higher efficacy outweigh risks of vaccine-associated paralysis. UK switched to IPV in 2004
- Sabin oral polio vaccine (OPV) = live-attenuated
- Viable virus can be recovered from stool after immunisation
- Highly effective, and also establishes some protection in non-immunised population
- 1 in 750 000 vaccine-associated paralytic polio
- Salk injected polio vaccine (IPV) = inactivated
- Effective, but herd immunity inferior
- OPV better suited to endemic areas, where benefits of higher efficacy outweigh risks of vaccine-associated paralysis. UK switched to IPV in 2004
Salk vs Sabin Polio - Vaccines
- Sabin oral polio vaccine (OPV) = live-attenuated
- Viable virus can be recovered from stool after immunisation
- … effective, and also establishes some protection in non-immunised population
- 1 in … vaccine-associated paralytic polio
- Salk injected polio vaccine (IPV) = inactivated
- Effective, but herd immunity …
- OPV better suited to endemic areas, where benefits of higher efficacy outweigh risks of vaccine-associated paralysis. UK switched to IPV in 2004
- Sabin oral polio vaccine (OPV) = live-attenuated
- Viable virus can be recovered from stool after immunisation
- Highly effective, and also establishes some protection in non-immunised population
- 1 in 750 000 vaccine-associated paralytic polio
- Salk injected polio vaccine (IPV) = inactivated
- Effective, but herd immunity inferior
- OPV better suited to endemic areas, where benefits of higher efficacy outweigh risks of vaccine-associated paralysis. UK switched to IPV in 2004
OPV vs IPV polio vaccines
- … over (…) better suited to endemic areas, where benefits of higher efficacy outweigh risks of vaccine-associated paralysis.
- UK switched to … in 2004
- OPV (Sabin oral polio vaccine) over Salk injected polio vaccine (IPV) better suited to endemic areas, where benefits of higher efficacy outweigh risks of vaccine-associated paralysis.
- UK switched to IPV in 2004
Tuberculosis
- During primary infection, MTB establishes infection within phago-lysosomes of … These present TB antigen to MTB-specific CD4 T cells, which secrete IFN-g – this activates … to encase TB in granuloma.
- May be visible as a calcified lesion on plain CXR (Ghon focus)
- Most TB thought to be re-activation of this primary infection

- During primary infection, MTB establishes infection within phago-lysosomes of macrophages. Macrophages present TB antigen to MTB-specific CD4 T cells, which secrete IFN-g – this activates macrophages to encase TB in granuloma.
- May be visible as a calcified lesion on plain CXR (Ghon focus)
- Most TB thought to be re-activation of this primary infection
Tuberculosis
- During primary infection, MTB establishes infection within phago-lysosomes of macrophages. Macrophages present TB antigen to MTB-specific … T cells, which secrete IFN-g – this activates macrophages to encase TB in granuloma.
- May be visible as a calcified lesion on plain CXR (Ghon focus)
- Most TB thought to be …-… of this primary infection

- During primary infection, MTB establishes infection within phago-lysosomes of macrophages. Macrophages present TB antigen to MTB-specific CD4 T cells, which secrete IFN-g – this activates macrophages to encase TB in granuloma.
- May be visible as a calcified lesion on plain CXR (Ghon focus)
- Most TB thought to be re-activation of this primary infection
Tuberculosis may be visible as a … lesion on plain CXR (Ghon focus)
Tuberculosis may be visible as a calcified lesion on plain CXR (Ghon focus)
During primary infection (TB), MTB establishes infection within phago-lysosomes of macrophages. Macrophages present TB antigen to MTB-specific CD4 T cells, which secrete …-g – this activates macrophages to encase TB in granuloma.
During primary infection, MTB establishes infection within phago-lysosomes of macrophages. Macrophages present TB antigen to MTB-specific CD4 T cells, which secrete IFN-g – this activates macrophages to encase TB in granuloma.
Most TB thought to be … of this primary infection
Most TB thought to be re-activation of this primary infection
TB vaccination
- Only licensed product is …
- Produced by repeat passage of a non-tuberculus mycobacterium: Mycobacterium bovis
- Aims to increase Th1 (IFN-g) cell responses to M bovis, thereby conferring protection against MTB
- Given by … injection
- 80% effective in preventing disseminated TB/ TB meningitis in children; little or no effect on pulmonary TB
- Only licensed product is BCG (bacille Calmette-Guerin)
- Produced by repeat passage of a non-tuberculus mycobacterium: Mycobacterium bovis
- Aims to increase Th1 (IFN-g) cell responses to M bovis, thereby conferring protection against MTB
- Given by intradermal injection
- 80% effective in preventing disseminated TB/ TB meningitis in children; little or no effect on pulmonary TB
TB vaccination
- Only licensed product is BCG (bacille Calmette-Guerin)
- Produced by repeat passage of a non-tuberculus mycobacterium: Mycobacterium bovis
- Aims to increase Th1 (…-g) cell responses to M bovis, thereby conferring protection against MTB
- Given by intradermal injection
- …% effective in preventing disseminated TB/ TB meningitis in children; little or no effect on pulmonary TB
- Only licensed product is BCG (bacille Calmette-Guerin)
- Produced by repeat passage of a non-tuberculus mycobacterium: Mycobacterium bovis
- Aims to increase Th1 (IFN-g) cell responses to M bovis, thereby conferring protection against MTB
- Given by intradermal injection
- 80% effective in preventing disseminated TB/ TB meningitis in children; little or no effect on pulmonary TB
TB vaccination is 80% effective in preventing … TB/ TB meningitis in children; little or no effect on … TB
TB vaccination is 80% effective in preventing disseminated TB/ TB meningitis in children; little or no effect on pulmonary TB
TB vaccination is …% effective in preventing disseminated TB/ TB meningitis in …; little or no effect on pulmonary TB
TB vaccination is 80% effective in preventing disseminated TB/ TB meningitis in children; little or no effect on pulmonary TB
Killed (inactivated) vaccines
- Entire organism used, but physical or chemical methods used to destroy … (eg formaldehyde)
- Stimulates B cells, and taken up by …-… cells to stimulate antigen-specific CD4 T cells
- Probably elicit minimal … response, as the vaccine cannot undergo intracellular replication
- Responses less robust compared to live-attenuated vaccines
- Examples
- Hepatitis A
- Influenza (standard vaccine – live-attenuated also available but not routinely used)
- Entire organism used, but physical or chemical methods used to destroy viability (eg formaldehyde)
- Stimulates B cells, and taken up by antigen-presenting cells to stimulate antigen-specific CD4 T cells
- Probably elicit minimal CD8 response, as the vaccine cannot undergo intracellular replication
- Responses less robust compared to live-attenuated vaccines
- Examples
- Hepatitis A
- Influenza (standard vaccine – live-attenuated also available but not routinely used)
Killed (inactivated) vaccines
- Entire organism used, but physical or chemical methods used to destroy viability (eg formaldehyde)
- Stimulates B cells, and taken up by antigen-presenting cells to stimulate antigen-specific … T cells
- Probably elicit minimal … response, as the vaccine cannot undergo intracellular replication
- Responses … robust compared to live-attenuated vaccines
- Examples
- Hepatitis A
- Influenza (standard vaccine – live-attenuated also available but not routinely used)
- Entire organism used, but physical or chemical methods used to destroy viability (eg formaldehyde)
- Stimulates B cells, and taken up by antigen-presenting cells to stimulate antigen-specific CD4 T cells
- Probably elicit minimal CD8 response, as the vaccine cannot undergo intracellular replication
- Responses less robust compared to live-attenuated vaccines
- Examples
- Hepatitis A
- Influenza (standard vaccine – live-attenuated also available but not routinely used)
Killed (inactivated) vaccines
- Entire organism used, but physical or chemical methods used to destroy viability (eg formaldehyde)
- Stimulates B cells, and taken up by antigen-presenting cells to stimulate antigen-specific CD4 T cells
- Probably elicit minimal CD8 response, as the vaccine cannot undergo intracellular replication
- Responses less robust compared to live-attenuated vaccines
- Examples
- … A
- … (standard vaccine – live-attenuated also available but not routinely used)
- Entire organism used, but physical or chemical methods used to destroy viability (eg formaldehyde)
- Stimulates B cells, and taken up by antigen-presenting cells to stimulate antigen-specific CD4 T cells
- Probably elicit minimal CD8 response, as the vaccine cannot undergo intracellular replication
- Responses less robust compared to live-attenuated vaccines
- Examples
- Hepatitis A
- Influenza (standard vaccine – live-attenuated also available but not routinely used)
Killed (inactivated) vaccines
- … organism used, but physical or chemical methods used to destroy viability (eg formaldehyde)
- Stimulates B cells, and taken up by antigen-presenting cells to stimulate antigen-specific CD4 T cells
- Probably elicit minimal CD8 response, as the vaccine cannot undergo intracellular replication
- Responses less robust compared to live-attenuated vaccines
- Examples
- Hepatitis …
- Influenza (standard vaccine – live-attenuated also available but not routinely used)
- Entire organism used, but physical or chemical methods used to destroy viability (eg formaldehyde)
- Stimulates B cells, and taken up by antigen-presenting cells to stimulate antigen-specific CD4 T cells
- Probably elicit minimal CD8 response, as the vaccine cannot undergo intracellular replication
- Responses less robust compared to live-attenuated vaccines
- Examples
- Hepatitis A
- Influenza (standard vaccine – live-attenuated also available but not routinely used)
Pros and cons of killed vaccines
- No potential for …
- Safe for …
- Stable in storage
- Weaker responses compared to live vaccines, and no CD8 response, therefore
- Responses less durable then live vaccines
- Generally boosters required
- Higher uptake generally required to achieve herd immunity
- No potential for reversion
- Safe for immunocompromised
- Stable in storage
- Weaker responses compared to live vaccines, and no CD8 response, therefore
- Responses less durable then live vaccines
- Generally boosters required
- Higher uptake generally required to achieve herd immunity
Pros and cons of killed vaccines
- No potential for reversion
- Safe for immunocompromised
- Stable in …
- … responses compared to live vaccines, and no CD8 response, therefore
- Responses less durable then live vaccines
- Generally boosters required
- Higher uptake generally required to achieve herd immunity
- No potential for reversion
- Safe for immunocompromised
- Stable in storage
- Weaker responses compared to live vaccines, and no CD8 response, therefore
- Responses less durable then live vaccines
- Generally boosters required
- Higher uptake generally required to achieve herd immunity
Pros and cons of killed vaccines
- No potential for reversion
- Safe for immunocompromised
- Stable in storage
- Weaker responses compared to live vaccines, and no … response, therefore
- Responses less … then live vaccines
- Generally boosters required
- Higher uptake generally required to achieve herd immunity
- No potential for reversion
- Safe for immunocompromised
- Stable in storage
- Weaker responses compared to live vaccines, and no CD8 response, therefore
- Responses less durable then live vaccines
- Generally boosters required
- Higher uptake generally required to achieve herd immunity
Pros and cons of killed vaccines
- No potential for reversion
- Safe for immunocompromised
- Stable in storage
- Weaker responses compared to live vaccines, and no CD8 response, therefore
- Responses less durable then live vaccines
- Generally … required
- Higher uptake generally required to achieve … …
- No potential for reversion
- Safe for immunocompromised
- Stable in storage
- Weaker responses compared to live vaccines, and no CD8 response, therefore
- Responses less durable then live vaccines
- Generally boosters required
- Higher uptake generally required to achieve herd immunity
Influenza
- … viral illness
- Protective antibody responses largely directed against haemagglutinin (H) and neuramidase (N) surface antigens
- Natural antigenic ‘…’ each year means that protective immune response from previous years may not be protective
- Major antigenic ‘…’ when virus recombines with animal influenza strain – eg ‘Spanish’ Influenza (1918), H1N1 (2009)
- Seasonal viral illness
- Protective antibody responses largely directed against haemagglutinin (H) and neuramidase (N) surface antigens
- Natural antigenic ‘drift’ each year means that protective immune response from previous years may not be protective
- Major antigenic ‘shift’ when virus recombines with animal influenza strain – eg ‘Spanish’ Influenza (1918), H1N1 (2009)

Influenza
- Seasonal viral illness
- Protective antibody responses largely directed against … (H) and neuramidase (N) surface antigens
- Natural antigenic ‘drift’ each year means that protective immune response from previous years may not be …
- Major antigenic ‘shift’ when virus … with animal influenza strain – eg ‘Spanish’ Influenza (1918), H1N1 (2009)
- Seasonal viral illness
- Protective antibody responses largely directed against haemagglutinin (H) and neuramidase (N) surface antigens
- Natural antigenic ‘drift’ each year means that protective immune response from previous years may not be protective
- Major antigenic ‘shift’ when virus recombines with animal influenza strain – eg ‘Spanish’ Influenza (1918), H1N1 (2009)

Influenza - Vaccine
- As immune responses are not durable, CDC attempts to predict likely … viruses for next season
- Candidate viruses grown in hens eggs and distributed to manufacturers
- … vaccine is standard UK approach
- … vaccine also available (nasal spray)
- Success varies from year to year
- As immune responses are not durable, CDC attempts to predict likely dominant viruses for next season
- Candidate viruses grown in hens eggs and distributed to manufacturers
- Killed vaccine is standard UK approach
- Live vaccine also available (nasal spray)
- Success varies from year to year
Influenza - Vaccine
- As immune responses are not …, CDC attempts to predict likely dominant viruses for next season
- Candidate viruses grown in hens eggs and distributed to manufacturers
- Killed vaccine is standard UK approach
- Live vaccine also available (nasal spray)
- Success … from year to year
- As immune responses are not durable, CDC attempts to predict likely dominant viruses for next season
- Candidate viruses grown in hens eggs and distributed to manufacturers
- Killed vaccine is standard UK approach
- Live vaccine also available (nasal spray)
- Success varies from year to year
Subunit vaccines
- Uses only a … part of the organism
- Components may be:
- … from the organism or
- generated by recombinant techniques
- Protection depends on eliciting CD4 and antibody responses
- Uses only a critical part of the organism
- Components may be:
- purified from the organism or
- generated by recombinant techniques
- Protection depends on eliciting CD4 and antibody responses
Subunit vaccines
- Uses only a critical part of the organism
- Components may be:
- purified from the organism or
- generated by … techniques
- Protection depends on eliciting … and antibody responses
- Uses only a critical part of the organism
- Components may be:
- purified from the organism or
- generated by recombinant techniques
- Protection depends on eliciting CD4 and antibody responses
Subunit vaccines: toxoids
- Many examples relate to …-producing bacteria
- Corynebacterium diphtheriae
- Clostridium tetani
- Bordatella pertussis
- … are chemically detoxified to ‘toxoids’
- Retain immunogenicity
- Work by stimulating antibody response; antibodies then neutralise the toxin
- Many examples relate to toxin-producing bacteria
- Corynebacterium diphtheriae
- Clostridium tetani
- Bordatella pertussis
- Toxins are chemically detoxified to ‘toxoids’
- Retain immunogenicity
- Work by stimulating antibody response; antibodies then neutralise the toxin
Subunit vaccines: toxoids
- Many examples relate to toxin-producing bacteria
- Corynebacterium diphtheriae
- Clostridium tetani
- Bordatella pertussis
- Toxins are chemically detoxified to ‘toxoids’
- Retain …
- Work by stimulating … response; … then neutralise the toxin
- Many examples relate to toxin-producing bacteria
- Corynebacterium diphtheriae
- Clostridium tetani
- Bordatella pertussis
- Toxins are chemically detoxified to ‘toxoids’
- Retain immunogenicity
- Work by stimulating antibody response; antibodies then neutralise the toxin
Examples of toxoid vaccine (Subunit vaccine) (3)
- Corynebacterium diphtheriae
- Clostridium tetani
- Bordatella pertussis
Tetanus
- Pre-formed high-affinity … antibodies can … the toxin molecules in the circulation; the immune complexes are then removed via the …
- Anti-toxin can also be given in established cases (passive immunisation)
- Pre-formed high-affinity IgG antibodies can neutralise the toxin molecules in the circulation; the immune complexes are then removed via the spleen
- Anti-toxin can also be given in established cases (passive immunisation)

Tetanus
- Pre-formed high-affinity IgG antibodies can … the toxin molecules in the circulation; the immune complexes are then removed via the spleen
- …-toxin can also be given in established cases (… immunisation)
- Pre-formed high-affinity IgG antibodies can neutralise the toxin molecules in the circulation; the immune complexes are then removed via the spleen
- Anti-toxin can also be given in established cases (passive immunisation)

Subunit vaccines: polysaccharide capsules
- Thick polysaccharide coats of Streptococcus … and Neisseria … make them resistant to …
- Vaccines for these organisms formed of purified polysaccharide coats
- Vaccines formed of purified polysaccharide coats; aim to induce IgG antibodies that improve opsonisation
- Suboptimal as polysaccharides are weakly immunogenic:
- No protein/ peptide, so no T cell response
- Stimulate a small population of T-independent B cells
- Latest vaccines utilise vaccine conjugation to boost responses: protein carrier attached to polysaccharide antigen
- Thick polysaccharide coats of Streptococcus pneumoniae and Neisseria meningitidis make them resistant to phagocytosis
- Vaccines for these organisms formed of purified polysaccharide coats
- Vaccines formed of purified polysaccharide coats; aim to induce IgG antibodies that improve opsonisation
- Suboptimal as polysaccharides are weakly immunogenic:
- No protein/ peptide, so no T cell response
- Stimulate a small population of T-independent B cells
- Latest vaccines utilise vaccine conjugation to boost responses: protein carrier attached to polysaccharide antigen
Subunit vaccines: polysaccharide capsules
- Thick polysaccharide coats of … pneumoniae and … meningitidis make them resistant to phagocytosis
- Vaccines for these organisms formed of purified polysaccharide coats
- Vaccines formed of purified polysaccharide coats; aim to induce … antibodies that improve opsonisation
- Suboptimal as … are weakly …:
- No protein/ peptide, so no T cell response
- Stimulate a small population of T-independent B cells
- Latest vaccines utilise vaccine conjugation to boost responses: protein carrier attached to polysaccharide antigen
- Thick polysaccharide coats of Streptococcus pneumoniae and Neisseria meningitidis make them resistant to phagocytosis
- Vaccines for these organisms formed of purified polysaccharide coats
- Vaccines formed of purified polysaccharide coats; aim to induce IgG antibodies that improve opsonisation
- Suboptimal as polysaccharides are weakly immunogenic:
- No protein/ peptide, so no T cell response
- Stimulate a small population of T-independent B cells
- Latest vaccines utilise vaccine conjugation to boost responses: protein carrier attached to polysaccharide antigen
Subunit vaccines: polysaccharide capsules
- Thick polysaccharide coats of Streptococcus pneumoniae and Neisseria meningitidis make them resistant to phagocytosis
- Vaccines for these organisms formed of purified polysaccharide coats
- Vaccines formed of purified polysaccharide coats; aim to induce IgG antibodies that improve …
- Suboptimal as polysaccharides are weakly immunogenic:
- No p../p… so no T cell response
- Stimulate a small population of T-… B cells
- Latest vaccines utilise vaccine conjugation to boost responses: protein carrier attached to polysaccharide antigen
- Thick polysaccharide coats of Streptococcus pneumoniae and Neisseria meningitidis make them resistant to phagocytosis
- Vaccines for these organisms formed of purified polysaccharide coats
- •Vaccines formed of purified polysaccharide coats; aim to induce IgG antibodies that improve opsonisation
- Suboptimal as polysaccharides are weakly immunogenic:
- No protein/ peptide, so no T cell response
- Stimulate a small population of T-independent B cells
- Latest vaccines utilise vaccine conjugation to boost responses: protein carrier attached to polysaccharide antigen
Vaccine conjugation
- Naive B cell (T-… B cell) expressing surface Ig… recognises … antigen. Antigen is internalised together with the protein …
- Conjugate is processed in the class II pathway. Naive B cell presents peptides from the conjugate to a helper T cell with the correct receptor.
- T cell helps the B cell to perform affinity maturation, but antibody is specific for the polysaccharide and not for the protein conjugate
- Naive B cell (T-independent B cell) expressing surface IgM recognises polysaccharide antigen. Antigen is internalised together with the protein conjugate
- Conjugate is processed in the class II pathway. Naive B cell presents peptides from the conjugate to a helper T cell with the correct receptor.
- T cell helps the B cell to perform affinity maturation, but antibody is specific for the polysaccharide and not for the protein conjugate

Vaccine conjugation
- Naive B cell (T-independent B cell) expressing surface IgM recognises polysaccharide antigen. Antigen is internalised together with the protein conjugate
- Conjugate is processed in the class … pathway. Naive B cell presents peptides from the conjugate to a … T cell with the correct receptor.
- T cell helps the B cell to perform affinity maturation, but antibody is specific for the polysaccharide and not for the protein conjugate
- Naive B cell (T-independent B cell) expressing surface IgM recognises polysaccharide antigen. Antigen is internalised together with the protein conjugate
- Conjugate is processed in the class II pathway. Naive B cell presents peptides from the conjugate to a helper T cell with the correct receptor.
- T cell helps the B cell to perform affinity maturation, but antibody is specific for the polysaccharide and not for the protein conjugate

Vaccine conjugation
- Naive B cell (T-independent B cell) expressing surface IgM recognises polysaccharide antigen. Antigen is internalised together with the protein conjugate
- Conjugate is processed in the class II pathway. Naive B cell presents peptides from the conjugate to a helper T cell with the correct receptor.
- T cell helps the B cell to perform … maturation, but antibody is specific for the … and not for the … conjugate
- Naive B cell (T-independent B cell) expressing surface IgM recognises polysaccharide antigen. Antigen is internalised together with the protein conjugate
- Conjugate is processed in the class II pathway. Naive B cell presents peptides from the conjugate to a helper T cell with the correct receptor.
- T cell helps the B cell to perform affinity maturation, but antibody is specific for the polysaccharide and not for the protein conjugate

Subunit vaccines: polysaccharide capsules
- Latest vaccines utilise vaccine … to boost responses: … carrier attached to … antigen
Latest vaccines utilise vaccine conjugation to boost responses: protein carrier attached to polysaccharide antigen
Recombinant protein subunit vaccine
- Knowledge of key immunogenic proteins required
- Proteins expressed in … organisms
- Purified to produce vaccine
- Hepatitis … surface antigen
- … vaccine
- This approach is increasingly employed in vaccine development
- Knowledge of key immunogenic proteins required
- Proteins expressed in lower organisms
- Purified to produce vaccine
- Hepatitis B surface antigen
- HPV vaccine
- This approach is increasingly employed in vaccine development
Recombinant protein subunit vaccine
- Knowledge of key immunogenic … required
- Proteins expressed in lower organisms
- … to produce vaccine
- Hepatitis B surface antigen
- HPV vaccine
- This approach is increasingly employed in vaccine development
- Knowledge of key immunogenic proteins required
- Proteins expressed in lower organisms
-
Purified to produce vaccine
- Hepatitis B surface antigen
- HPV vaccine
- This approach is increasingly employed in vaccine development
Human papilloma virus vaccination
- HPV subtypes … and … infection major causal factor in cervical carcinoma
- Vaccine development problematic as HPV is difficult to …
- Subunit vaccines are ‘empty virus particles’ that prevent primary infection
- Quadravalent vaccine covers additional HPV strains (genital warts, penile cancer)
- HPV subtypes 16 and 18 infection major causal factor in cervical carcinoma
- Vaccine development problematic as HPV is difficult to culture
- Subunit vaccines are ‘empty virus particles’ that prevent primary infection
- Quadravalent vaccine covers additional HPV strains (genital warts, penile cancer)

Human papilloma virus vaccination
- HPV subtypes 16 and 18 infection major causal factor in cervical …
- Vaccine development problematic as HPV is difficult to culture
- Subunit vaccines are ‘… virus particles’ that prevent primary infection
- Quadravalent vaccine covers additional HPV strains (genital warts, penile cancer)
- HPV subtypes 16 and 18 infection major causal factor in cervical carcinoma
- Vaccine development problematic as HPV is difficult to culture
- Subunit vaccines are ‘empty virus particles’ that prevent primary infection
- Quadravalent vaccine covers additional HPV strains (genital warts, penile cancer)

Human papilloma virus vaccination
- HPV subtypes 16 and 18 infection major causal factor in cervical carcinoma
- Vaccine development problematic as HPV is difficult to culture
- … vaccines are ‘empty virus particles’ that prevent … infection
- … vaccine covers additional HPV strains (genital warts, penile cancer)
- HPV subtypes 16 and 18 infection major causal factor in cervical carcinoma
- Vaccine development problematic as HPV is difficult to culture
- Subunit vaccines are ‘empty virus particles’ that prevent primary infection
- Quadravalent vaccine covers additional HPV strains (genital warts, penile cancer)

Pros and cons of subunit vaccines
- Extremely …
- Work well where primary infection may be prevented by an … response
- Works when the virus cannot easily be cultured eg HPV and Hep B
- Development requires detailed knowledge of virology, pathogenesis and immunology
- Specialised and expensive production
- Weaker immune responses – boosting often needed and response rate varies
- Extremely safe
- Work well where primary infection may be prevented by an antibody response
- Works when the virus cannot easily be cultured eg HPV and Hep B
- Development requires detailed knowledge of virology, pathogenesis and immunology
- Specialised and expensive production
- Weaker immune responses – boosting often needed and response rate varies
Pros and cons of subunit vaccines
- Extremely safe
- Work well where primary infection may be prevented by an antibody response
- Works when the virus cannot easily be … eg HPV and Hep B
- Development requires detailed knowledge of virology, pathogenesis and immunology
- Specialised and expensive production
- Weaker immune responses – … often needed and response rate varies
- Extremely safe
- Work well where primary infection may be prevented by an antibody response
- Works when the virus cannot easily be cultured eg HPV and Hep B
- Development requires detailed knowledge of virology, pathogenesis and immunology
- Specialised and expensive production
- Weaker immune responses – boosting often needed and response rate varies
Pros and cons of subunit vaccines
- Extremely safe
- Work well where primary infection may be prevented by an antibody response
- Works when the virus cannot easily be cultured eg HPV and Hep B
- Development requires detailed knowledge of virology, pathogenesis and immunology
- … and … production
- Weaker immune responses – boosting often needed and … rate varies
- Extremely safe
- Work well where primary infection may be prevented by an antibody response
- Works when the virus cannot easily be cultured eg HPV and Hep B
- Development requires detailed knowledge of virology, pathogenesis and immunology
- Specialised and expensive production
- Weaker immune responses – boosting often needed and response rate varies
Adjuvants
- … immune response to the antigen
- … used, but mechanism understood only relatively recently
- Eg alum, lipopolysaccharide
- Work by binding to pattern-recognition receptors on antigen presenting cells
- This enhances co-stimulation and cytokine secretion, which ensures a robust T/ B cell response
- Important field for development in order to improve responses to subunit vaccines
- Novel adjuvants are toll-like receptor ligands eg CPG repeats
- Boost immune response to the antigen
-
Widely used, but mechanism understood only relatively recently
- Eg alum, lipopolysaccharide
- Work by binding to pattern-recognition receptors on antigen presenting cells
- This enhances co-stimulation and cytokine secretion, which ensures a robust T/ B cell response
- Important field for development in order to improve responses to subunit vaccines
- Novel adjuvants are toll-like receptor ligands eg CPG repeats
Adjuvants
- Boost immune response to the antigen
- Widely used, but mechanism understood only relatively recently
- Eg alum, lipopolysaccharide
- Work by binding to …-… receptors on antigen presenting cells
- This enhances co-… and … secretion, which ensures a robust T/ B cell response
- Important field for development in order to improve responses to subunit vaccines
- Novel adjuvants are toll-like receptor ligands eg CPG repeats
- Boost immune response to the antigen
- Widely used, but mechanism understood only relatively recently
- Eg alum, lipopolysaccharide
- Work by binding to pattern-recognition receptors on antigen presenting cells
- This enhances co-stimulation and cytokine secretion, which ensures a robust T/ B cell response
- Important field for development in order to improve responses to subunit vaccines
- Novel adjuvants are toll-like receptor ligands eg CPG repeats
Adjuvants
- Boost immune response to the antigen
- Widely used, but mechanism understood only relatively recently
- Eg alum, lipopolysaccharide
- Work by binding to pattern-recognition receptors on antigen presenting cells
- This enhances co-stimulation and cytokine secretion, which ensures a robust T/ B cell response
- Important field for development in order to improve responses to … vaccines
- Novel adjuvants are …-… receptor ligands eg CPG repeats
- Boost immune response to the antigen
- Widely used, but mechanism understood only relatively recently
- Eg alum, lipopolysaccharide
- Work by binding to pattern-recognition receptors on antigen presenting cells
- This enhances co-stimulation and cytokine secretion, which ensures a robust T/ B cell response
- Important field for development in order to improve responses to subunit vaccines
- Novel adjuvants are toll-like receptor ligands eg CPG repeats
Novel adjuvants are …-like receptor ligands eg CPG repeats
Novel adjuvants are toll-like receptor ligands eg CPG repeats
How do Adjuvants work?
Work by binding to pattern-recognition receptors on antigen presenting cells
Give an example of an adjuvant
alum
New approaches: mRNA vaccines
- For mRNA vaccines, sequence generated which codes for critical pathogen antigens
- Delivered via … eg lipid nanoparticles OR … vivo (harvest circulating monocytes then return to recipient)
- Sequence translated by host cells to produce encoded antigens, which then stimulates host immune response
- In development since …
- Key technical challenges
- Preventing degradation of mRNA – solution was lipid nanoparticle delivery
- Inflammatory response caused by mRNA – solution was modifying nucleosides
- Potentially rapidly available and modifiable; relatively quick and easy to produce and adapt once facility established
- Utilised in new SARS-CoV2 vaccines made by Pfizer and Moderna; mRNA codes for viral spike protein
- For mRNA vaccines, sequence generated which codes for critical pathogen antigens
- Delivered via vector eg lipid nanoparticles OR ex vivo (harvest circulating monocytes then return to recipient)
- Sequence translated by host cells to produce encoded antigens, which then stimulates host immune response
- In development since 1990s
- Key technical challenges
- Preventing degradation of mRNA – solution was lipid nanoparticle delivery
- Inflammatory response caused by mRNA – solution was modifying nucleosides
- Potentially rapidly available and modifiable; relatively quick and easy to produce and adapt once facility established
- Utilised in new SARS-CoV2 vaccines made by Pfizer and Moderna; mRNA codes for viral spike protein
New approaches: mRNA vaccines
- For mRNA vaccines, … generated which codes for critical … antigens
- Delivered via vector eg lipid nanoparticles OR ex vivo (harvest circulating monocytes then return to recipient)
- Sequence translated by host cells to produce encoded antigens, which then stimulates host immune response
- In development since 1990s
- Key technical challenges
- Preventing … of mRNA – solution was lipid nanoparticle delivery
- … response caused by mRNA – solution was modifying nucleosides
- Potentially rapidly available and modifiable; relatively quick and easy to produce and adapt once facility established
- Utilised in new SARS-CoV2 vaccines made by Pfizer and Moderna; mRNA codes for viral spike protein
- For mRNA vaccines, sequence generated which codes for critical pathogen antigens
- Delivered via vector eg lipid nanoparticles OR ex vivo (harvest circulating monocytes then return to recipient)
- Sequence translated by host cells to produce encoded antigens, which then stimulates host immune response
- In development since 1990s
- Key technical challenges
- Preventing degradation of mRNA – solution was lipid nanoparticle delivery
- Inflammatory response caused by mRNA – solution was modifying nucleosides
- Potentially rapidly available and modifiable; relatively quick and easy to produce and adapt once facility established
- Utilised in new SARS-CoV2 vaccines made by Pfizer and Moderna; mRNA codes for viral spike protein
New approaches: mRNA vaccines
- For mRNA vaccines, sequence generated which codes for critical pathogen antigens
- Delivered via vector eg lipid nanoparticles OR ex vivo (harvest circulating monocytes then return to recipient)
- Sequence translated by host cells to produce encoded antigens, which then stimulates host immune response
- In development since 1990s
- Key technical challenges
- Preventing degradation of mRNA – solution was lipid … delivery
- Inflammatory response caused by mRNA – solution was modifying nucleosides
- Potentially rapidly available and modifiable; relatively quick and easy to produce and adapt once facility established
- Utilised in new SARS-CoV2 vaccines made by … and …; mRNA codes for viral spike protein
- For mRNA vaccines, sequence generated which codes for critical pathogen antigens
- Delivered via vector eg lipid nanoparticles OR ex vivo (harvest circulating monocytes then return to recipient)
- Sequence translated by host cells to produce encoded antigens, which then stimulates host immune response
- In development since 1990s
- Key technical challenges
- Preventing degradation of mRNA – solution was lipid nanoparticle delivery
- Inflammatory response caused by mRNA – solution was modifying nucleosides
- Potentially rapidly available and modifiable; relatively quick and easy to produce and adapt once facility established
- Utilised in new SARS-CoV2 vaccines made by Pfizer and Moderna; mRNA codes for viral spike protein
mRNA Vaccine - How does it work?

Novel approaches: viral vector
- … virus that can be easily grown in culture engineered to carry genes encoding … antigens
- Altered virus used as a live-attenuated vaccine or a non-replicating viral vaccine
- Challenges
- Pre-existing immunity to viral vector
- Immune responses to viral vector may affect later use
- … SARS-CoV2 vaccine utilises replication-deficient Simian adenovirus carrying spike protein gene
- Russian Sputnik V vaccine uses similar approach, but with two different replication-deficient human adenovirus vectors – one for priming, one for boosting
- Johnson and Johnson product is another replication-deficient simian adenoviral vector; trialled to demonstrate single-dose protection
- Benign virus that can be easily grown in culture engineered to carry genes encoding immunogenic antigens
- Altered virus used as a live-attenuated vaccine or a non-replicating viral vaccine
- Challenges
- Pre-existing immunity to viral vector
- Immune responses to viral vector may affect later use
- Astra-Zenica SARS-CoV2 vaccine utilises replication-deficient Simian adenovirus carrying spike protein gene
- Russian Sputnik V vaccine uses similar approach, but with two different replication-deficient human adenovirus vectors – one for priming, one for boosting
- Johnson and Johnson product is another replication-deficient simian adenoviral vector; trialled to demonstrate single-dose protection
Novel approaches: viral vector
- Benign virus that can be easily grown in culture engineered to carry genes encoding immunogenic antigens
- Altered virus used as a live-attenuated vaccine or a non-replicating viral vaccine
- Challenges
- Pre-existing … to viral vector
- Immune responses to viral vector may affect … use
- Astra-Zenica SARS-CoV2 vaccine utilises replication-deficient Simian adenovirus carrying spike protein gene
- Russian Sputnik V vaccine uses similar approach, but with two different replication-deficient human adenovirus vectors – one for priming, one for boosting
- Johnson and Johnson product is another replication-deficient simian adenoviral vector; trialled to demonstrate single-dose protection
- Benign virus that can be easily grown in culture engineered to carry genes encoding immunogenic antigens
- Altered virus used as a live-attenuated vaccine or a non-replicating viral vaccine
- Challenges
- Pre-existing immunity to viral vector
- Immune responses to viral vector may affect later use
- Astra-Zenica SARS-CoV2 vaccine utilises replication-deficient Simian adenovirus carrying spike protein gene
- Russian Sputnik V vaccine uses similar approach, but with two different replication-deficient human adenovirus vectors – one for priming, one for boosting
- Johnson and Johnson product is another replication-deficient simian adenoviral vector; trialled to demonstrate single-dose protection
Novel approaches: viral vector
- Benign virus that can be easily grown in culture engineered to carry genes encoding immunogenic antigens
- Altered virus used as a live-attenuated vaccine or a non-replicating viral vaccine
- Challenges
- Pre-existing immunity to viral vector
- Immune responses to viral vector may affect later use
- Astra-Zenica SARS-CoV2 vaccine utilises replication-deficient Simian adenovirus carrying … protein gene
- Russian Sputnik V vaccine uses similar approach, but with two different replication-deficient human adenovirus vectors – one for …, one for boosting
- Johnson and Johnson product is another replication-deficient simian adenoviral vector; trialled to demonstrate …-dose protection
- Benign virus that can be easily grown in culture engineered to carry genes encoding immunogenic antigens
- Altered virus used as a live-attenuated vaccine or a non-replicating viral vaccine
- Challenges
- Pre-existing immunity to viral vector
- Immune responses to viral vector may affect later use
- Astra-Zenica SARS-CoV2 vaccine utilises replication-deficient Simian adenovirus carrying spike protein gene
- Russian Sputnik V vaccine uses similar approach, but with two different replication-deficient human adenovirus vectors – one for priming, one for boosting
- Johnson and Johnson product is another replication-deficient simian adenoviral vector; trialled to demonstrate single-dose protection
Example of lenteviral vaccine transduction

Recombinant protein subunit vaccine examples (2)
Hep B and HPV
Hepatitis B is what type of vaccine?
Recombinant protein subunit vaccine