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

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2
Q

What is Immunisation?

A

Immunisation is an artificial process by which an individual is rendered immune

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3
Q

… immunisation – no immune response in recipient

A

Passive immunisation – no immune response in recipient

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4
Q

… immunisation (…) – recipient develops a protective adaptive immune response

A

Active immunisation (vaccination) – recipient develops a protective adaptive immune response

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5
Q

Passive vs Active Immunisation

A
  • Passive immunisation – no immune response in recipient
  • Active immunisation (vaccination) – recipient develops a protective adaptive immune response
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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

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7
Q

Immunisation estimated reduction in mortality worldwide … million/ yr

A

Immunisation estimated reduction in mortality worldwide 3 million/ yr

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8
Q

Variola = … virus

A

Variola =smallpox virus

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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)
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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
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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
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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
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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
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14
Q

Is passive immunisation protection permanent or temporary?

A

temporary

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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
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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
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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
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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
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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

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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
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21
Q

Active immunisation is the same as …

A

Active immunisation (vaccination)

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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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)
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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
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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
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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
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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
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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
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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
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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
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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
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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
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43
Q

The varicella-zoster vaccine is …% effective at preventing chickenpox

A

95% effective at preventing chickenpox

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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
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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
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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
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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