Vaccines Flashcards
1
Q
Immunisation is an … process by which an individual is rendered …
A
Immunisation is an artificial process by which an individual is rendered immune
2
Q
What is Immunisation?
A
Immunisation is an artificial process by which an individual is rendered immune
3
Q
… immunisation – no immune response in recipient
A
Passive immunisation – no immune response in recipient
4
Q
… immunisation (…) – recipient develops a protective adaptive immune response
A
Active immunisation (vaccination) – recipient develops a protective adaptive immune response
5
Q
Passive vs Active Immunisation
A
- Passive immunisation – no immune response in recipient
- Active immunisation (vaccination) – recipient develops a protective adaptive immune response
6
Q
Immunisation is one of the cheapest and most effective methods of improving … and reducing …
A
Immunisation is one of the cheapest and most effective methods of improving survival and reducing morbidity
7
Q
Immunisation estimated reduction in mortality worldwide … million/ yr
A
Immunisation estimated reduction in mortality worldwide 3 million/ yr
8
Q
Variola = … virus
A
Variola =smallpox virus
9
Q
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)
A
- 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)
10
Q
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
A
- 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
11
Q
- 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
A
- 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
12
Q
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
A
- 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
13
Q
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 …
A
- 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
14
Q
Is passive immunisation protection permanent or temporary?
A
temporary
15
Q
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
A
- 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
16
Q
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
A
- 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
17
Q
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
A
- 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
18
Q
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
A
- 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
19
Q
In pregnant women with no history of chickenpox or unsure, do bloods to check for VZV IgG - If positive, what does that mean?
A
Reassure - they are immune, if negative this means they have not had chickenpox before and give VZV immunoglobulin
20
Q
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
A
- 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
21
Q
Active immunisation is the same as …
A
Active immunisation (vaccination)
22
Q
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
A
- 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
23
Q
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
A
- 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
24
Q
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
A
- 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
25
Q
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
A
-
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
26
Q
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
A
- 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
27
Q
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
A
- 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
28
Q
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
A
- 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
29
Q
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
A
- 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
30
Q
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 …
A
- 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
31
Q
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
A
- 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
32
Q
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 …
A
- 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
33
Q
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)
A
- 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)
34
Q
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
A
- 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
35
Q
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
A
- 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
36
Q
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
A
- 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
37
Q
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
A
- 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
38
Q
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
A
- 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
39
Q
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
A
- 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
40
Q
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
A
- 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
41
Q
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
A
- 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
42
Q
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
A
- 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
43
Q
The varicella-zoster vaccine is …% effective at preventing chickenpox
A
95% effective at preventing chickenpox
44
Q
Is VZV (Varicella-Zoster vaccine) on UK vaccination schedule?
A
- 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
45
Q
Zoster, immunity and aging
- The incidence of zoster … with age, in parallel with … cell-mediated immune responses to zoster
A
- The incidence of zoster increases with age, in parallel with declining cell-mediated immune responses to zoster
46
Q
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
A
- 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
47
Q
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
A
- 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
48
Q
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
A
- 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
49
Q
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
A
- 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
50
Q
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
A
- 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
51
Q
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
A
- 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
52
Q
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 …
A
- 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
53
Q
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
A
- 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
54
Q
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
A
- 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
55
Q
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
A
- 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
56
Q
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
A
- 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
57
Q
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
A
- 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
58
Q
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
A
- 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
59
Q
Tuberculosis may be visible as a … lesion on plain CXR (Ghon focus)
A
Tuberculosis may be visible as a calcified lesion on plain CXR (Ghon focus)
60
Q
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.
A
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.
61
Q
Most TB thought to be … of this primary infection
A
Most TB thought to be re-activation of this primary infection
62
Q
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
A
- 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
63
Q
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
A
- 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
64
Q
TB vaccination is 80% effective in preventing … TB/ TB meningitis in children; little or no effect on … TB
A
TB vaccination is 80% effective in preventing disseminated TB/ TB meningitis in children; little or no effect on pulmonary TB
65
Q
TB vaccination is …% effective in preventing disseminated TB/ TB meningitis in …; little or no effect on pulmonary TB
A
TB vaccination is 80% effective in preventing disseminated TB/ TB meningitis in children; little or no effect on pulmonary TB
66
Q
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)
A
- 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)
67
Q
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)
A
- 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)
68
Q
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)
A
- 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)
69
Q
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)
A
- 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)
70
Q
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
A
- 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
71
Q
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
A
- 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
72
Q
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
A
- 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
73
Q
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 … …
A
- 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
74
Q
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)
A
- 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)
75
Q
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)
A
- 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)
76
Q
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
A
- 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
77
Q
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
A
- 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
78
Q
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
A
- 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
79
Q
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
A
- 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
80
Q
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
A
- 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
81
Q
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
A
- 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
82
Q
Examples of toxoid vaccine (Subunit vaccine) (3)
A
- Corynebacterium diphtheriae
- Clostridium tetani
- Bordatella pertussis
83
Q
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)
A
- 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)
84
Q
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)
A
- 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)
85
Q
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
A
- 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
86
Q
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
A
- 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
87
Q
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
A
- 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
88
Q
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
A
- 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
89
Q
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
A
- 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
90
Q
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
A
- 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
91
Q
Subunit vaccines: polysaccharide capsules
- Latest vaccines utilise vaccine … to boost responses: … carrier attached to … antigen
A
Latest vaccines utilise vaccine conjugation to boost responses: protein carrier attached to polysaccharide antigen
92
Q
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
A
- 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
93
Q
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
A
- 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
94
Q
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)
A
- 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)
95
Q
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)
A
- 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)
96
Q
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)
A
- 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)
97
Q
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
A
- 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
98
Q
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
A
- 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
99
Q
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
A
- 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
100
Q
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
A
- 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
101
Q
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
A
- 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
102
Q
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
A
- 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
103
Q
Novel adjuvants are …-like receptor ligands eg CPG repeats
A
Novel adjuvants are toll-like receptor ligands eg CPG repeats
104
Q
How do Adjuvants work?
A
Work by binding to pattern-recognition receptors on antigen presenting cells
105
Q
Give an example of an adjuvant
A
alum
106
Q
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
A
- 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
107
Q
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
A
- 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
108
Q
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
A
- 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
109
Q
mRNA Vaccine - How does it work?
A
110
Q
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
A
- 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
111
Q
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
A
- 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
112
Q
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
A
- 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
113
Q
Example of lenteviral vaccine transduction
A
114
Q
Recombinant protein subunit vaccine examples (2)
A
Hep B and HPV
115
Q
Hepatitis B is what type of vaccine?
A
Recombinant protein subunit vaccine
