Year 2 Medicine > Vaccines > Flashcards

Vaccines Flashcards

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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
_What goes into a vaccine?_ * ... * To stimulate an ...-specific T and B cell response * ... * Immune potentiators to increase the immunogenicity of the vaccine * ‘Excipients’ * Various diluents and additives required for vaccine integrity
* **Antigen** * To stimulate an **antigen**-specific T and B cell response * **Adjuvants** * Immune potentiators to increase the immunogenicity of the vaccine * ‘Excipients’ * Various diluents and additives required for vaccine integrity
26
_What goes into a vaccine?_ * Antigen * To ... an antigen-specific T and B cell response * Adjuvants * Immune potentiators to increase the immunogenicity of the vaccine * ‘...’ * Various diluents and additives required for vaccine integrity
* Antigen * To **stimulate** an antigen-specific T and B cell response * Adjuvants * Immune potentiators to increase the immunogenicity of the vaccine * ‘**Excipients**’ * Various diluents and additives required for vaccine integrity
27
_Classification of active vaccines on the basis of the antigen_ * Active Vaccines - divided into ... organism or subunit * ... organism * Live-attenuated vaccine * Inactivated (killed) * S.. * Toxoids * Capsular polysaccharide * Conjugated polysaccharide * Recombinant subunit * ?mRNA, VLPs, viral vector
* Active Vaccines - divided into **whole** **organism** or subunit * **Whole** **organism** * Live-attenuated vaccine * Inactivated (killed) * **Subunit** * Toxoids * Capsular polysaccharide * Conjugated polysaccharide * Recombinant subunit * ?mRNA, VLPs, viral vector
28
_Classification of active vaccines on the basis of the antigen_ * Active Vaccines - divided into whole organism or subunit * Whole organism * ...-... vaccine * Inactivated (killed) * Subunit * T... * Capsular polysaccharide * Conjugated polysaccharide * Recombinant subunit * ?mRNA, VLPs, viral vector
* Active Vaccines - divided into whole organism or subunit * Whole organism * **Live-attenuated** vaccine * Inactivated (killed) * Subunit * **Toxoids** * Capsular polysaccharide * Conjugated polysaccharide * Recombinant subunit * ?mRNA, VLPs, viral vector
29
_Classification of active vaccines on the basis of the antigen_ * Active Vaccines - divided into whole organism or subunit * Whole organism * Live-attenuated vaccine * ... (killed) * Subunit * Toxoids * C.. polysaccharide * C... polysaccharide * Recombinant subunit * ?mRNA, VLPs, viral vector
* Active Vaccines - divided into whole organism or subunit * Whole organism * Live-attenuated vaccine * **Inactivated** (killed) * Subunit * Toxoids * **Capsular** polysaccharide * **Conjugated** polysaccharide * Recombinant subunit * ?mRNA, VLPs, viral vector
30
_Classification of active vaccines on the basis of the antigen_ * Active Vaccines - divided into whole organism or subunit * Whole organism * Live-attenuated vaccine * Inactivated (killed) * Subunit * Toxoids * Capsular polysaccharide * Conjugated polysaccharide * ... subunit * ?..RNA, VLPs, viral ...
* Active Vaccines - divided into whole organism or subunit * Whole organism * Live-attenuated vaccine * Inactivated (killed) * Subunit * Toxoids * Capsular polysaccharide * Conjugated polysaccharide * **Recombinant** subunit * ?**mRNA**, VLPs, viral **vector**
31
_Live-attenuated vaccines_ * Live but attenuated organisms used * Prolonged culture ... vivo in non-... conditions * This selects variants that are adapted to live in ... * These variants are viable in vivo but are no longer able to cause disease
* Live but attenuated organisms used * Prolonged culture **ex** vivo in non-**physiological** conditions * This selects variants that are adapted to live in **culture** * These variants are viable in vivo but are no longer able to cause disease
32
_Live-attenuated vaccines_ * Live but attenuated organisms used * Prolonged culture ex vivo in non-physiological conditions * This selects variants that are adapted to live in culture * These variants are viable ... vivo but are no longer able to cause ...
* Live but attenuated organisms used * Prolonged culture ex vivo in non-physiological conditions * This selects variants that are adapted to live in culture * These variants are viable **in** vivo but are no longer able to cause **disease**
33
_Examples of Live-attenuated vaccines_ * M... * M... * R... * P... (Sabin) * B... * Cholera * Zoster * VZV (not routinely used for primary prevention in UK at present) * Live influenza (not main product in UK at present)
* **Measles** * **Mumps** * **Rubella** * **Polio (Sabin)** * **BCG** * Cholera * Zoster * VZV (not routinely used for primary prevention in UK at present) * Live influenza (not main product in UK at present)
34
_Pros and cons of live vaccines_ * + Replication ... ..., therefore produces highly effective and durable responses * + In case of viral vaccine, intracellular infection leads to good ... response * + Repeated ... not required * + In some diseases, may get secondary protection of unvaccinated individuals, who are infected with the live-attenuated vaccine strain eg polio * - Storage problems, short shelf-life * - May revert to wild type Eg vaccine associated poliomyelitis: around 1 in 750 000 recipients * - Immunocompromised recipients may develop clinical disease
* + Replication **within host**, therefore produces highly effective and durable responses * + In case of viral vaccine, intracellular infection leads to good **CD8** response * + Repeated **boosting** not required * + In some diseases, may get secondary protection of unvaccinated individuals, who are infected with the live-attenuated vaccine strain eg polio * - Storage problems, short shelf-life * - May revert to wild type Eg vaccine associated poliomyelitis: around 1 in 750 000 recipients * - Immunocompromised recipients may develop clinical disease
35
_Pros and cons of live vaccines_ * + Replication within host, therefore produces highly effective and durable responses * + In case of viral vaccine, intracellular infection leads to good CD8 response * + Repeated boosting not required * + In some diseases, may get ... protection of ... individuals, who are infected with the live-attenuated vaccine strain eg polio * - ... problems, short ...-life * - May revert to wild type Eg vaccine associated poliomyelitis: around 1 in 750 000 recipients * - Immunocompromised recipients may develop clinical disease
* + Replication within host, therefore produces highly effective and durable responses * + In case of viral vaccine, intracellular infection leads to good CD8 response * + Repeated boosting not required * + In some diseases, may get **secondary** protection of **unvaccinated** individuals, who are infected with the live-attenuated vaccine strain eg polio * - **Storage** problems, short **shelf**-life * - May revert to wild type Eg vaccine associated poliomyelitis: around 1 in 750 000 recipients * - Immunocompromised recipients may develop clinical disease
36
_Pros and cons of live vaccines_ * + Replication within host, therefore produces highly effective and durable responses * + In case of viral vaccine, intracellular infection leads to good CD8 response * + Repeated boosting not required * + In some diseases, may get secondary protection of unvaccinated individuals, who are infected with the live-attenuated vaccine strain eg polio * - Storage problems, short shelf-life * - May revert to ... type Eg vaccine associated poliomyelitis: around 1 in 750 000 recipients * - ... recipients may develop clinical disease
* + Replication within host, therefore produces highly effective and durable responses * + In case of viral vaccine, intracellular infection leads to good CD8 response * + Repeated boosting not required * + In some diseases, may get secondary protection of unvaccinated individuals, who are infected with the live-attenuated vaccine strain eg polio * - Storage problems, short shelf-life * - May revert to **wild** type Eg vaccine associated poliomyelitis: around 1 in 750 000 recipients * - **Immunocompromised** recipients may develop clinical disease
37
_Varicella-Zoster Vaccine_ * Primary infection = ... * Cellular and humoral immunity provide lifelong protection, but viruses establishes permanent infection of sensory ganglia * Viral reactivation= ... * Particularly elderly, fairly debilitating and may cause long-term neuropathic pain
* Primary infection = **chickenpox** * Cellular and humoral immunity provide lifelong protection, but viruses establishes permanent infection of sensory ganglia * Viral reactivation= **zoster (shingles)** * Particularly elderly, fairly debilitating and may cause long-term neuropathic pain
38
_Varicella-Zoster Vaccine_ * Primary infection = chickenpox * Cellular and humoral immunity provide ... protection, but viruses establishes ... infection of sensory ganglia * Viral ... = zoster (shingles) * Particularly elderly, fairly debilitating and may cause long-term neuropathic pain
* Primary infection = chickenpox * Cellular and humoral immunity provide **lifelong** protection, but viruses establishes **permanent** infection of sensory ganglia * Viral **reactivation**=zoster (shingles) * Particularly elderly, fairly debilitating and may cause long-term neuropathic pain
39
_Varicella-Zoster Vaccine_ * Primary infection = ... * Cellular and humoral immunity provide lifelong protection, but viruses establishes permanent infection of sensory ganglia * Viral reactivation= Zoster (shingles) * Particularly ..., fairly ... and may cause long-term ... pain
* Primary infection = **chickenpox** * Cellular and humoral immunity provide lifelong protection, but viruses establishes permanent infection of sensory ganglia * Viral reactivation= **zoster (shingles)** * Particularly **elderly**, fairly **debilitating** and may cause long-term **neuropathic** pain
40
_Varicella-Zoster Vaccine_ * ...-... VZV, works by induction of anti-VZV antibodies * ...% effective at preventing chickenpox * Attenuated virus does establish infection of sensory ganglia, but subsequent zoster is probably rare * ..-..% mild post-vaccination varicella infection * Not on UK schedule at present, because: * VZV is a fairly benign childhood infection * ?Schedule is already crowded and controversial * Safety concerns based on evidence from other countries * ‘Disease shift’ to unvaccinated adults, in whom VZV is less well tolerated * Increase in zoster – probably reduced immune boosting in adults
* **Live-attenuated** VZV, works by induction of anti-VZV antibodies * **95**% effective at preventing chickenpox * Attenuated virus does establish infection of sensory ganglia, but subsequent zoster is probably rare * **3-5**% mild post-vaccination varicella infection * Not on UK schedule at present, because: * VZV is a fairly benign childhood infection * ?Schedule is already crowded and controversial * Safety concerns based on evidence from other countries * ‘Disease shift’ to unvaccinated adults, in whom VZV is less well tolerated * Increase in zoster – probably reduced immune boosting in adults
41
_Varicella-Zoster Vaccine_ * Live-attenuated VZV, works by induction of anti-VZV antibodies * 95% effective at preventing chickenpox * Attenuated virus does establish infection of sensory ..., but subsequent zoster is probably rare * 3-5% mild post-vaccination varicella infection * Not on UK schedule at present, because: * VZV is a fairly ... childhood infection * ?Schedule is already crowded and c... * ... concerns based on evidence from other countries * ‘Disease shift’ to unvaccinated adults, in whom VZV is less well tolerated * Increase in zoster – probably reduced immune boosting in adults
* Live-attenuated VZV, works by induction of anti-VZV antibodies * 95% effective at preventing chickenpox * Attenuated virus does establish infection of sensory **ganglia**, but subsequent zoster is probably rare * 3-5% mild post-vaccination varicella infection * Not on UK schedule at present, because: * VZV is a fairly **benign** childhood infection * ?Schedule is already crowded and **controversial** * **Safety** concerns based on evidence from other countries * ‘Disease shift’ to unvaccinated adults, in whom VZV is less well tolerated * Increase in zoster – probably reduced immune boosting in adults
42
_Varicella-Zoster Vaccine_ * Live-attenuated VZV, works by induction of anti-VZV antibodies * 95% effective at preventing chickenpox * Attenuated virus does establish infection of sensory ganglia, but subsequent zoster is probably rare * 3-5% mild post-vaccination varicella infection * Not on UK schedule at present, because: * VZV is a fairly benign childhood infection * ?Schedule is already crowded and controversial * Safety concerns based on evidence from other countries * ‘... shift’ to unvaccinated adults, in whom VZV is less well tolerated * Increase in ... – probably reduced immune boosting in adults
* Live-attenuated VZV, works by induction of anti-VZV antibodies * 95% effective at preventing chickenpox * Attenuated virus does establish infection of sensory ganglia, but subsequent zoster is probably rare * 3-5% mild post-vaccination varicella infection * Not on UK schedule at present, because: * VZV is a fairly benign childhood infection * ?Schedule is already crowded and controversial * Safety concerns based on evidence from other countries * ‘**Disease** shift’ to unvaccinated adults, in whom VZV is less well tolerated * Increase in **zoster** – probably reduced immune boosting in adults
43
The varicella-zoster vaccine is ...% effective at preventing chickenpox
**95% effective at preventing chickenpox**
44
Is VZV (Varicella-Zoster vaccine) on UK vaccination schedule?
* Not on UK schedule at present, because: * VZV is a fairly benign childhood infection * ?Schedule is already crowded and controversial * Safety concerns based on evidence from other countries * ‘Disease shift’ to unvaccinated adults, in whom VZV is less well tolerated * Increase in zoster – probably reduced immune boosting in adults
45
_Zoster, immunity and aging_ * The incidence of zoster ... with age, in parallel with ... cell-mediated immune responses to zoster
* The incidence of zoster **increases** with age, in parallel with **declining** cell-mediated immune responses to zoster
46
_Zoster vaccination_ * Similar VZV preparation to that used for ... disease, but much ... dose * Aims to boost memory T cell responses to VZV * In over 60s, 50% reduction in zoster incidence after vaccination compared to controls; reduced severity and complications amongst vaccinated cases
* Similar VZV preparation to that used for **primary** disease, but much **higher** dose * Aims to boost memory T cell responses to VZV * In over 60s, 50% reduction in zoster incidence after vaccination compared to controls; reduced severity and complications amongst vaccinated cases
47
_Zoster vaccination_ * Similar VZV preparation to that used for primary disease, but much ... dose * Aims to boost ... T cell responses to VZV * In over 60s, 50% reduction in zoster incidence after vaccination compared to controls; reduced severity and complications amongst vaccinated cases
* Similar VZV preparation to that used for primary disease, but much **higher** dose * Aims to boost **memory** T cell responses to VZV * In over 60s, 50% reduction in zoster incidence after vaccination compared to controls; reduced severity and complications amongst vaccinated cases
48
_Zoster vaccination_ * Similar VZV preparation to that used for ... disease, but much ... dose * Aims to boost memory T cell responses to VZV * In over 60s, ...% reduction in zoster incidence after vaccination compared to controls; reduced severity and complications amongst vaccinated cases
* Similar VZV preparation to that used for **primary** disease, but much **higher** dose * Aims to boost memory T cell responses to VZV * In over 60s, **50**% reduction in zoster incidence after vaccination compared to controls; reduced severity and complications amongst vaccinated cases
49
_Zoster vaccination_ * Similar VZV preparation to that used for primary disease, but much ... dose * Aims to boost memory T cell responses to VZV * In over 60s, 50% reduction in zoster incidence after vaccination compared to controls; reduced ... and ... amongst vaccinated cases
* Similar VZV preparation to that used for **primary** disease, but much **higher** dose * Aims to boost memory T cell responses to VZV * In over 60s, 50% reduction in zoster incidence after vaccination compared to controls; reduced **severity** and **complications** amongst vaccinated cases
50
_Poliomyelitis_ * ...virus establishes infection in ... and GI tract (alimentary phase) * Spreads to peyers patches then disseminated via lymphatics * Haematogenous spread (viremia phase) * ...% of patients develop neurological phase: replication in motor neurones in spinal cord, brainstem and motor cortex, leading to denervation and flaccid paralysis
* **Enterovirus** establishes infection in **oropharynx** and GI tract (alimentary phase) * Spreads to peyers patches then disseminated via lymphatics * Haematogenous spread (viremia phase) * **1**% of patients develop neurological phase: replication in motor neurones in spinal cord, brainstem and motor cortex, leading to denervation and flaccid paralysis
51
_Poliomyelitis_ * Enterovirus establishes infection in oropharynx and ... tract (... phase) * Spreads to peyers patches then disseminated via lymphatics * Haematogenous spread (viremia phase) * 1% of patients develop ... phase: replication in motor neurones in spinal cord, brainstem and motor cortex, leading to denervation and flaccid paralysis
* Enterovirus establishes infection in oropharynx and **GI** tract (**alimentary** phase) * Spreads to peyers patches then disseminated via lymphatics * Haematogenous spread (viremia phase) * 1% of patients develop **neurological** phase: replication in motor neurones in spinal cord, brainstem and motor cortex, leading to denervation and flaccid paralysis
52
_Poliomyelitis_ * Enterovirus establishes infection in oropharynx and GI tract (alimentary phase) * Spreads to peyers patches then disseminated via lymphatics * Haematogenous spread (... phase) * 1% of patients develop neurological phase: replication in motor neurones in spinal cord, brainstem and motor cortex, leading to denervation and flaccid ...
* Enterovirus establishes infection in oropharynx and GI tract (alimentary phase) * Spreads to peyers patches then disseminated via lymphatics * Haematogenous spread (**viremia** phase) * 1% of patients develop neurological phase: replication in motor neurones in spinal cord, brainstem and motor cortex, leading to denervation and flaccid **paralysis**
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_Poliomyelitis_ * Enterovirus establishes infection in oropharynx and GI tract (alimentary phase) * Spreads to ... patches then disseminated via lymphatics * ... spread (viremia phase) * 1% of patients develop neurological phase: replication in motor neurones in spinal cord, brainstem and motor cortex, leading to denervation and flaccid paralysis
* Enterovirus establishes infection in oropharynx and GI tract (alimentary phase) * Spreads to **peyers** patches then disseminated via lymphatics * **Haematogenous** spread (viremia phase) * 1% of patients develop neurological phase: replication in motor neurones in spinal cord, brainstem and motor cortex, leading to denervation and flaccid paralysis
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_Salk vs Sabin Polio - Vaccines_ * Sabin oral polio vaccine (OPV) = ...-... * Viable virus can be recovered from stool after immunisation * Highly effective, and also establishes some protection in non-immunised population * 1 in 750 000 vaccine-associated paralytic polio * Salk injected polio vaccine (IPV) = ... * Effective, but herd immunity inferior * OPV better suited to endemic areas, where benefits of higher efficacy outweigh risks of vaccine-associated paralysis. UK switched to IPV in 2004
* Sabin oral polio vaccine (OPV) = **live-attenuated** * Viable virus can be recovered from stool after immunisation * Highly effective, and also establishes some protection in non-immunised population * 1 in 750 000 vaccine-associated paralytic polio * Salk injected polio vaccine (IPV) = **inactivated** * Effective, but herd immunity inferior * OPV better suited to endemic areas, where benefits of higher efficacy outweigh risks of vaccine-associated paralysis. UK switched to IPV in 2004
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_Salk vs Sabin Polio - Vaccines_ * Sabin oral polio vaccine (OPV) = live-attenuated * Viable virus can be recovered from stool after immunisation * ... effective, and also establishes some protection in non-immunised population * 1 in ... vaccine-associated paralytic polio * Salk injected polio vaccine (IPV) = inactivated * Effective, but herd immunity ... * OPV better suited to endemic areas, where benefits of higher efficacy outweigh risks of vaccine-associated paralysis. UK switched to IPV in 2004
* Sabin oral polio vaccine (OPV) = live-attenuated * Viable virus can be recovered from stool after immunisation * Highly **effective**, and also establishes some protection in non-immunised population * 1 in **750 000** vaccine-associated paralytic polio * Salk injected polio vaccine (IPV) = inactivated * Effective, but herd immunity **inferior** * OPV better suited to endemic areas, where benefits of higher efficacy outweigh risks of vaccine-associated paralysis. UK switched to IPV in 2004
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_OPV vs IPV polio vaccines_ * ... over (...) better suited to endemic areas, where benefits of higher efficacy outweigh risks of vaccine-associated paralysis. * UK switched to ... in 2004
* **OPV** (Sabin oral polio vaccine) over Salk injected polio vaccine (**IPV**) better suited to endemic areas, where benefits of higher efficacy outweigh risks of vaccine-associated paralysis. * UK switched to **IPV** in 2004
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_Tuberculosis_ * During primary infection, MTB establishes infection within phago-lysosomes of ... These present TB antigen to MTB-specific CD4 T cells, which secrete IFN-g – this activates ... to encase TB in granuloma. * May be visible as a calcified lesion on plain CXR (Ghon focus) * Most TB thought to be re-activation of this primary infection
* During primary infection, MTB establishes infection within phago-lysosomes of **macrophages**. **Macrophages** present TB antigen to MTB-specific CD4 T cells, which secrete IFN-g – this activates **macrophages** to encase TB in granuloma. * May be visible as a calcified lesion on plain CXR (Ghon focus) * Most TB thought to be re-activation of this primary infection
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_Tuberculosis_ * During primary infection, MTB establishes infection within phago-lysosomes of macrophages. Macrophages present TB antigen to MTB-specific ... T cells, which secrete IFN-g – this activates macrophages to encase TB in granuloma. * May be visible as a calcified lesion on plain CXR (Ghon focus) * Most TB thought to be ...-... of this primary infection
* During primary infection, MTB establishes infection within phago-lysosomes of macrophages. Macrophages present TB antigen to MTB-specific **CD4** T cells, which secrete IFN-g – this activates macrophages to encase TB in granuloma. * May be visible as a calcified lesion on plain CXR (Ghon focus) * Most TB thought to be **re-activation** of this primary infection
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Tuberculosis may be visible as a ... lesion on plain CXR (Ghon focus)
Tuberculosis may be visible as a **calcified** lesion on plain CXR (Ghon focus)
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During primary infection (TB), MTB establishes infection within phago-lysosomes of macrophages. Macrophages present TB antigen to MTB-specific CD4 T cells, which secrete ...-g – this activates macrophages to encase TB in granuloma.
During primary infection, MTB establishes infection within phago-lysosomes of macrophages. Macrophages present TB antigen to MTB-specific CD4 T cells, which secrete **IFN**-g – this activates macrophages to encase TB in granuloma.
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Most TB thought to be **...** of this primary infection
Most TB thought to be **re-activation** of this primary infection
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_TB vaccination_ * Only licensed product is ... * Produced by repeat passage of a non-tuberculus mycobacterium: Mycobacterium bovis * Aims to increase Th1 (IFN-g) cell responses to M bovis, thereby conferring protection against MTB * Given by ... injection * 80% effective in preventing disseminated TB/ TB meningitis in children; little or no effect on pulmonary TB
* Only licensed product is **BCG (bacille Calmette-Guerin)** * Produced by repeat passage of a non-tuberculus mycobacterium: Mycobacterium bovis * Aims to increase Th1 (IFN-g) cell responses to M bovis, thereby conferring protection against MTB * Given by **intradermal** injection * 80% effective in preventing disseminated TB/ TB meningitis in children; little or no effect on pulmonary TB
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_TB vaccination_ * Only licensed product is BCG (bacille Calmette-Guerin) * Produced by repeat passage of a non-tuberculus mycobacterium: Mycobacterium bovis * Aims to increase Th1 (...-g) cell responses to M bovis, thereby conferring protection against MTB * Given by intradermal injection * ...% effective in preventing disseminated TB/ TB meningitis in children; little or no effect on pulmonary TB
* Only licensed product is BCG (bacille Calmette-Guerin) * Produced by repeat passage of a non-tuberculus mycobacterium: Mycobacterium bovis * Aims to increase Th1 (**IFN**-g) cell responses to M bovis, thereby conferring protection against MTB * Given by intradermal injection * **80**% effective in preventing disseminated TB/ TB meningitis in children; little or no effect on pulmonary TB
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TB vaccination is 80% effective in preventing ... TB/ TB meningitis in children; little or no effect on ... TB
TB vaccination is 80% effective in preventing **disseminated** TB/ TB meningitis in children; little or no effect on **pulmonary** TB
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TB vaccination is ...% effective in preventing disseminated TB/ TB meningitis in ...; little or no effect on pulmonary TB
TB vaccination is **80**% effective in preventing disseminated TB/ TB meningitis in **children**; little or no effect on pulmonary TB
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_Killed (inactivated) vaccines_ * Entire organism used, but physical or chemical methods used to destroy ... (eg formaldehyde) * Stimulates B cells, and taken up by ...-... cells to stimulate antigen-specific CD4 T cells * Probably elicit minimal ... response, as the vaccine cannot undergo intracellular replication * Responses less robust compared to live-attenuated vaccines * Examples * Hepatitis A * Influenza (standard vaccine – live-attenuated also available but not routinely used)
* Entire organism used, but physical or chemical methods used to destroy **viability** (eg formaldehyde) * Stimulates B cells, and taken up by **antigen-presenting** cells to stimulate antigen-specific CD4 T cells * Probably elicit minimal **CD8** response, as the vaccine cannot undergo intracellular replication * Responses less robust compared to live-attenuated vaccines * Examples * Hepatitis A * Influenza (standard vaccine – live-attenuated also available but not routinely used)
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_Killed (inactivated) vaccines_ * Entire organism used, but physical or chemical methods used to destroy viability (eg formaldehyde) * Stimulates B cells, and taken up by antigen-presenting cells to stimulate antigen-specific ... T cells * Probably elicit minimal ... response, as the vaccine cannot undergo intracellular replication * Responses ... robust compared to live-attenuated vaccines * Examples * Hepatitis A * Influenza (standard vaccine – live-attenuated also available but not routinely used)
* Entire organism used, but physical or chemical methods used to destroy viability (eg formaldehyde) * Stimulates B cells, and taken up by antigen-presenting cells to stimulate antigen-specific **CD4** T cells * Probably elicit minimal **CD8** response, as the vaccine cannot undergo intracellular replication * Responses **less** robust compared to live-attenuated vaccines * Examples * Hepatitis A * Influenza (standard vaccine – live-attenuated also available but not routinely used)
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_Killed (inactivated) vaccines_ * Entire organism used, but physical or chemical methods used to destroy viability (eg formaldehyde) * Stimulates B cells, and taken up by antigen-presenting cells to stimulate antigen-specific CD4 T cells * Probably elicit minimal CD8 response, as the vaccine cannot undergo intracellular replication * Responses less robust compared to live-attenuated vaccines * Examples * ... A * ... (standard vaccine – live-attenuated also available but not routinely used)
* Entire organism used, but physical or chemical methods used to destroy viability (eg formaldehyde) * Stimulates B cells, and taken up by antigen-presenting cells to stimulate antigen-specific CD4 T cells * Probably elicit minimal CD8 response, as the vaccine cannot undergo intracellular replication * Responses less robust compared to live-attenuated vaccines * Examples * **Hepatitis** A * **Influenza** (standard vaccine – live-attenuated also available but not routinely used)
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_Killed (inactivated) vaccines_ * ... organism used, but physical or chemical methods used to destroy viability (eg formaldehyde) * Stimulates B cells, and taken up by antigen-presenting cells to stimulate antigen-specific CD4 T cells * Probably elicit minimal CD8 response, as the vaccine cannot undergo intracellular replication * Responses less robust compared to live-attenuated vaccines * Examples * Hepatitis ... * Influenza (standard vaccine – live-attenuated also available but not routinely used)
* **Entire** organism used, but physical or chemical methods used to destroy viability (eg formaldehyde) * Stimulates B cells, and taken up by antigen-presenting cells to stimulate antigen-specific CD4 T cells * Probably elicit minimal CD8 response, as the vaccine cannot undergo intracellular replication * Responses less robust compared to live-attenuated vaccines * Examples * Hepatitis **A** * Influenza (standard vaccine – live-attenuated also available but not routinely used)
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_Pros and cons of killed vaccines_ * + No potential for ... * + Safe for ... * + Stable in storage * - Weaker responses compared to live vaccines, and no CD8 response, therefore * - Responses less durable then live vaccines * - Generally boosters required * - Higher uptake generally required to achieve herd immunity
* + No potential for **reversion** * + Safe for **immunocompromised** * + Stable in storage * - Weaker responses compared to live vaccines, and no CD8 response, therefore * - Responses less durable then live vaccines * - Generally boosters required * - Higher uptake generally required to achieve herd immunity
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_Pros and cons of killed vaccines_ * + No potential for reversion * + Safe for immunocompromised * + Stable in ... * - ... responses compared to live vaccines, and no CD8 response, therefore * - Responses less durable then live vaccines * - Generally boosters required * - Higher uptake generally required to achieve herd immunity
* + No potential for reversion * + Safe for immunocompromised * + Stable in **storage** * - **Weaker** responses compared to live vaccines, and no CD8 response, therefore * - Responses less durable then live vaccines * - Generally boosters required * - Higher uptake generally required to achieve herd immunity
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_Pros and cons of killed vaccines_ * + No potential for reversion * + Safe for immunocompromised * + Stable in storage * - Weaker responses compared to live vaccines, and no ... response, therefore * - Responses less ... then live vaccines * - Generally boosters required * - Higher uptake generally required to achieve herd immunity
* + No potential for reversion * + Safe for immunocompromised * + Stable in storage * - Weaker responses compared to live vaccines, and no **CD8** response, therefore * - Responses less **durable** then live vaccines * - Generally boosters required * - Higher uptake generally required to achieve herd immunity
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_Pros and cons of killed vaccines_ * + No potential for reversion * + Safe for immunocompromised * + Stable in storage * - Weaker responses compared to live vaccines, and no CD8 response, therefore * - Responses less durable then live vaccines * - Generally ... required * - Higher uptake generally required to achieve ... ...
* + No potential for reversion * + Safe for immunocompromised * + Stable in storage * - Weaker responses compared to live vaccines, and no CD8 response, therefore * - Responses less durable then live vaccines * - Generally **boosters** required * - Higher uptake generally required to achieve **herd immunity**
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_Influenza_ * ... viral illness * Protective antibody responses largely directed against haemagglutinin (H) and neuramidase (N) surface antigens * Natural antigenic ‘...’ each year means that protective immune response from previous years may not be protective * Major antigenic ‘...’ when virus recombines with animal influenza strain – eg ‘Spanish’ Influenza (1918), H1N1 (2009)
* **Seasonal** viral illness * Protective antibody responses largely directed against haemagglutinin (H) and neuramidase (N) surface antigens * Natural antigenic ‘**drift**’ each year means that protective immune response from previous years may not be protective * Major antigenic ‘sh**i**ft’ when virus recombines with animal influenza strain – eg ‘Spanish’ Influenza (1918), H1N1 (2009)
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_Influenza_ * Seasonal viral illness * Protective antibody responses largely directed against ... (H) and neuramidase (N) surface antigens * Natural antigenic ‘drift’ each year means that protective immune response from previous years may not be ... * Major antigenic ‘shift’ when virus ... with animal influenza strain – eg ‘Spanish’ Influenza (1918), H1N1 (2009)
* Seasonal viral illness * Protective antibody responses largely directed against **haemagglutinin** (H) and neuramidase (N) surface antigens * Natural antigenic ‘drift’ each year means that protective immune response from previous years may not be **protective** * Major antigenic ‘shift’ when virus **recombines** with animal influenza strain – eg ‘Spanish’ Influenza (1918), H1N1 (2009)
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_Influenza - Vaccine_ * As immune responses are not durable, CDC attempts to predict likely ... viruses for next season * Candidate viruses grown in hens eggs and distributed to manufacturers * ... vaccine is standard UK approach * ... vaccine also available (nasal spray) * Success varies from year to year
* As immune responses are not durable, CDC attempts to predict likely **dominant** viruses for next season * Candidate viruses grown in hens eggs and distributed to manufacturers * **Killed** vaccine is standard UK approach * **Live** vaccine also available (nasal spray) * Success varies from year to year
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_Influenza - Vaccine_ * As immune responses are not ..., CDC attempts to predict likely dominant viruses for next season * Candidate viruses grown in hens eggs and distributed to manufacturers * Killed vaccine is standard UK approach * Live vaccine also available (nasal spray) * Success ... from year to year
* As immune responses are not **durable**, CDC attempts to predict likely dominant viruses for next season * Candidate viruses grown in hens eggs and distributed to manufacturers * Killed vaccine is standard UK approach * Live vaccine also available (nasal spray) * Success **varies** from year to year
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_Subunit vaccines_ * Uses only a ... part of the organism * Components may be: * ... from the organism or * generated by recombinant techniques * Protection depends on eliciting CD4 and antibody responses
* Uses only a **critical** part of the organism * Components may be: * **purified** from the organism or * generated by recombinant techniques * Protection depends on eliciting CD4 and antibody responses
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_Subunit vaccines_ * Uses only a critical part of the organism * Components may be: * purified from the organism or * generated by ... techniques * Protection depends on eliciting ... and antibody responses
* Uses only a critical part of the organism * Components may be: * purified from the organism or * generated by **recombinant** techniques * Protection depends on eliciting **CD4** and antibody responses
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_Subunit vaccines: toxoids_ * Many examples relate to ...-producing bacteria * Corynebacterium diphtheriae * Clostridium tetani * Bordatella pertussis * ... are chemically detoxified to ‘toxoids’ * Retain immunogenicity * Work by stimulating antibody response; antibodies then neutralise the toxin
* Many examples relate to **toxin**-producing bacteria * Corynebacterium diphtheriae * Clostridium tetani * Bordatella pertussis * **Toxins** are chemically detoxified to ‘toxoids’ * Retain immunogenicity * Work by stimulating antibody response; antibodies then neutralise the toxin
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_Subunit vaccines: toxoids_ * Many examples relate to toxin-producing bacteria * Corynebacterium diphtheriae * Clostridium tetani * Bordatella pertussis * Toxins are chemically detoxified to ‘toxoids’ * Retain ... * Work by stimulating ... response; ... then neutralise the toxin
* Many examples relate to toxin-producing bacteria * Corynebacterium diphtheriae * Clostridium tetani * Bordatella pertussis * Toxins are chemically detoxified to ‘toxoids’ * Retain **immunogenicity** * Work by stimulating **antibody** response; **antibodies** then neutralise the toxin
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Examples of toxoid vaccine (Subunit vaccine) (3)
* Corynebacterium diphtheriae * Clostridium tetani * Bordatella pertussis
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_Tetanus_ * Pre-formed high-affinity ... antibodies can ... the toxin molecules in the circulation; the immune complexes are then removed via the ... * Anti-toxin can also be given in established cases (passive immunisation)
* Pre-formed high-affinity **IgG** antibodies can **neutralise** the toxin molecules in the circulation; the immune complexes are then removed via the **spleen** * Anti-toxin can also be given in established cases (passive immunisation)
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_Tetanus_ * Pre-formed high-affinity IgG antibodies can ... the toxin molecules in the circulation; the immune complexes are then removed via the spleen * ...-toxin can also be given in established cases (... immunisation)
* Pre-formed high-affinity IgG antibodies can **neutralise** the toxin molecules in the circulation; the immune complexes are then removed via the spleen * **Anti**-toxin can also be given in established cases (**passive** immunisation)
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_Subunit vaccines: polysaccharide capsules_ * Thick polysaccharide coats of Streptococcus ... and Neisseria ... make them resistant to ... * Vaccines for these organisms formed of purified polysaccharide coats * Vaccines formed of purified polysaccharide coats; aim to induce IgG antibodies that improve opsonisation * Suboptimal as polysaccharides are weakly immunogenic: * No protein/ peptide, so no T cell response * Stimulate a small population of T-independent B cells * Latest vaccines utilise vaccine conjugation to boost responses: protein carrier attached to polysaccharide antigen
* Thick polysaccharide coats of Streptococcus **pneumoniae** and Neisseria **meningitidis** make them resistant to **phagocytosis** * Vaccines for these organisms formed of purified polysaccharide coats * Vaccines formed of purified polysaccharide coats; aim to induce IgG antibodies that improve opsonisation * Suboptimal as polysaccharides are weakly immunogenic: * No protein/ peptide, so no T cell response * Stimulate a small population of T-independent B cells * Latest vaccines utilise vaccine conjugation to boost responses: protein carrier attached to polysaccharide antigen
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_Subunit vaccines: polysaccharide capsules_ * Thick polysaccharide coats of ... pneumoniae and ... meningitidis make them resistant to phagocytosis * Vaccines for these organisms formed of purified polysaccharide coats * Vaccines formed of purified polysaccharide coats; aim to induce ... antibodies that improve opsonisation * Suboptimal as ... are weakly ...: * No protein/ peptide, so no T cell response * Stimulate a small population of T-independent B cells * Latest vaccines utilise vaccine conjugation to boost responses: protein carrier attached to polysaccharide antigen
* Thick polysaccharide coats of **Streptococcus** pneumoniae and **Neisseria** meningitidis make them resistant to phagocytosis * Vaccines for these organisms formed of purified polysaccharide coats * Vaccines formed of purified polysaccharide coats; aim to induce **IgG** antibodies that improve opsonisation * Suboptimal as **polysaccharides** are weakly **immunogenic**: * No protein/ peptide, so no T cell response * Stimulate a small population of T-independent B cells * Latest vaccines utilise vaccine conjugation to boost responses: protein carrier attached to polysaccharide antigen
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_Subunit vaccines: polysaccharide capsules_ * Thick polysaccharide coats of Streptococcus pneumoniae and Neisseria meningitidis make them resistant to phagocytosis * Vaccines for these organisms formed of purified polysaccharide coats * Vaccines formed of purified polysaccharide coats; aim to induce IgG antibodies that improve ... * Suboptimal as polysaccharides are weakly immunogenic: * No p../p... so no T cell response * Stimulate a small population of T-... B cells * Latest vaccines utilise vaccine conjugation to boost responses: protein carrier attached to polysaccharide antigen
* Thick polysaccharide coats of Streptococcus pneumoniae and Neisseria meningitidis make them resistant to phagocytosis * Vaccines for these organisms formed of purified polysaccharide coats * •Vaccines formed of purified polysaccharide coats; aim to induce IgG antibodies that improve **opsonisation** * Suboptimal as polysaccharides are weakly immunogenic: * No **protein/ peptide**, so no T cell response * Stimulate a small population of T-**independent** B cells * Latest vaccines utilise vaccine conjugation to boost responses: protein carrier attached to polysaccharide antigen
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_Vaccine conjugation_ * Naive B cell (T-... B cell) expressing surface Ig... recognises ... antigen. Antigen is internalised together with the protein ... * Conjugate is processed in the class II pathway. Naive B cell presents peptides from the conjugate to a helper T cell with the correct receptor. * T cell helps the B cell to perform affinity maturation, but antibody is specific for the polysaccharide and not for the protein conjugate
* Naive B cell (T-**independent** B cell) expressing surface **IgM** recognises **polysaccharide** antigen. Antigen is internalised together with the protein **conjugate** * Conjugate is processed in the class II pathway. Naive B cell presents peptides from the conjugate to a helper T cell with the correct receptor. * T cell helps the B cell to perform affinity maturation, but antibody is specific for the polysaccharide and not for the protein conjugate
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_Vaccine conjugation_ * Naive B cell (T-independent B cell) expressing surface IgM recognises polysaccharide antigen. Antigen is internalised together with the protein conjugate * Conjugate is processed in the class ... pathway. Naive B cell presents peptides from the conjugate to a ... T cell with the correct receptor. * T cell helps the B cell to perform affinity maturation, but antibody is specific for the polysaccharide and not for the protein conjugate
* Naive B cell (T-independent B cell) expressing surface IgM recognises polysaccharide antigen. Antigen is internalised together with the protein conjugate * Conjugate is processed in the class **II** pathway. Naive B cell presents peptides from the conjugate to a **helper** T cell with the correct receptor. * T cell helps the B cell to perform affinity maturation, but antibody is specific for the polysaccharide and not for the protein conjugate
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_Vaccine conjugation_ * Naive B cell (T-independent B cell) expressing surface IgM recognises polysaccharide antigen. Antigen is internalised together with the protein conjugate * Conjugate is processed in the class II pathway. Naive B cell presents peptides from the conjugate to a helper T cell with the correct receptor. * T cell helps the B cell to perform ... maturation, but antibody is specific for the ... and not for the ... conjugate
* Naive B cell (T-independent B cell) expressing surface IgM recognises polysaccharide antigen. Antigen is internalised together with the protein conjugate * Conjugate is processed in the class II pathway. Naive B cell presents peptides from the conjugate to a helper T cell with the correct receptor. * T cell helps the B cell to perform **affinity** maturation, but antibody is specific for the **polysaccharide** and not for the **protein** conjugate
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_Subunit vaccines: polysaccharide capsules_ * Latest vaccines utilise vaccine ... to boost responses: ... carrier attached to ... antigen
Latest vaccines utilise vaccine **conjugation** to boost responses: **protein** carrier attached to **polysaccharide** antigen
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_Recombinant protein subunit vaccine_ * Knowledge of key immunogenic proteins required * Proteins expressed in ... organisms * Purified to produce vaccine * Hepatitis ... surface antigen * ... vaccine * This approach is increasingly employed in vaccine development
* Knowledge of key immunogenic proteins required * Proteins expressed in **lower** organisms * Purified to produce vaccine * Hepatitis **B** surface antigen * **HPV** vaccine * This approach is increasingly employed in vaccine development
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_Recombinant protein subunit vaccine_ * Knowledge of key immunogenic ... required * Proteins expressed in lower organisms * ... to produce vaccine * Hepatitis B surface antigen * HPV vaccine * This approach is increasingly employed in vaccine development
* Knowledge of key immunogenic **proteins** required * Proteins expressed in lower organisms * **Purified** to produce vaccine * Hepatitis B surface antigen * HPV vaccine * This approach is increasingly employed in vaccine development
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_Human papilloma virus vaccination_ * HPV subtypes ... and ... infection major causal factor in cervical carcinoma * Vaccine development problematic as HPV is difficult to ... * Subunit vaccines are ‘empty virus particles’ that prevent primary infection * Quadravalent vaccine covers additional HPV strains (genital warts, penile cancer)
* HPV subtypes **16** and **18** infection major causal factor in cervical carcinoma * Vaccine development problematic as HPV is difficult to **culture** * Subunit vaccines are ‘empty virus particles’ that prevent primary infection * Quadravalent vaccine covers additional HPV strains (genital warts, penile cancer)
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_Human papilloma virus vaccination_ * HPV subtypes 16 and 18 infection major causal factor in cervical ... * Vaccine development problematic as HPV is difficult to culture * Subunit vaccines are ‘... virus particles’ that prevent primary infection * Quadravalent vaccine covers additional HPV strains (genital warts, penile cancer)
* HPV subtypes 16 and 18 infection major causal factor in cervical **carcinoma** * Vaccine development problematic as HPV is difficult to culture * Subunit vaccines are ‘**empty** virus particles’ that prevent primary infection * Quadravalent vaccine covers additional HPV strains (genital warts, penile cancer)
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_Human papilloma virus vaccination_ * HPV subtypes 16 and 18 infection major causal factor in cervical carcinoma * Vaccine development problematic as HPV is difficult to culture * ... vaccines are ‘empty virus particles’ that prevent ... infection * ... vaccine covers additional HPV strains (genital warts, penile cancer)
* HPV subtypes 16 and 18 infection major causal factor in cervical carcinoma * Vaccine development problematic as HPV is difficult to culture * **Subunit** vaccines are ‘empty virus particles’ that prevent **primary** infection * **Quadravalent** vaccine covers additional HPV strains (genital warts, penile cancer)
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_Pros and cons of subunit vaccines_ * + Extremely ... * + Work well where primary infection may be prevented by an ... response * + Works when the virus cannot easily be cultured eg HPV and Hep B * - Development requires detailed knowledge of virology, pathogenesis and immunology * - Specialised and expensive production * - Weaker immune responses – boosting often needed and response rate varies
* + Extremely **safe** * + Work well where primary infection may be prevented by an **antibody** response * + Works when the virus cannot easily be cultured eg HPV and Hep B * - Development requires detailed knowledge of virology, pathogenesis and immunology * - Specialised and expensive production * - Weaker immune responses – boosting often needed and response rate varies
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_Pros and cons of subunit vaccines_ * + Extremely safe * + Work well where primary infection may be prevented by an antibody response * + Works when the virus cannot easily be ... eg HPV and Hep B * - Development requires detailed knowledge of virology, pathogenesis and immunology * - Specialised and expensive production * - Weaker immune responses – ... often needed and response rate varies
* + Extremely safe * + Work well where primary infection may be prevented by an antibody response * + Works when the virus cannot easily be **cultured** eg HPV and Hep B * - Development requires detailed knowledge of virology, pathogenesis and immunology * - Specialised and expensive production * - Weaker immune responses – **boosting** often needed and response rate varies
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_Pros and cons of subunit vaccines_ * + Extremely safe * + Work well where primary infection may be prevented by an antibody response * + Works when the virus cannot easily be cultured eg HPV and Hep B * - Development requires detailed knowledge of virology, pathogenesis and immunology * - ... and ... production * - Weaker immune responses – boosting often needed and ... rate varies
* + Extremely safe * + Work well where primary infection may be prevented by an antibody response * + Works when the virus cannot easily be cultured eg HPV and Hep B * - Development requires detailed knowledge of virology, pathogenesis and immunology * - **Specialised** and **expensive** production * - Weaker immune responses – boosting often needed and **response** rate varies
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_Adjuvants_ * ... immune response to the antigen * ... used, but mechanism understood only relatively recently * Eg alum, lipopolysaccharide * Work by binding to pattern-recognition receptors on antigen presenting cells * This enhances co-stimulation and cytokine secretion, which ensures a robust T/ B cell response * Important field for development in order to improve responses to subunit vaccines * Novel adjuvants are toll-like receptor ligands eg CPG repeats
* **Boost** immune response to the antigen * **Widely** used, but mechanism understood only relatively recently * Eg alum, lipopolysaccharide * Work by binding to pattern-recognition receptors on antigen presenting cells * This enhances co-stimulation and cytokine secretion, which ensures a robust T/ B cell response * Important field for development in order to improve responses to subunit vaccines * Novel adjuvants are toll-like receptor ligands eg CPG repeats
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_Adjuvants_ * Boost immune response to the antigen * Widely used, but mechanism understood only relatively recently * Eg alum, lipopolysaccharide * Work by binding to ...-... receptors on antigen presenting cells * This enhances co-... and ... secretion, which ensures a robust T/ B cell response * Important field for development in order to improve responses to subunit vaccines * Novel adjuvants are toll-like receptor ligands eg CPG repeats
* Boost immune response to the antigen * Widely used, but mechanism understood only relatively recently * Eg alum, lipopolysaccharide * Work by binding to **pattern-recognition** receptors on antigen presenting cells * This enhances co-**stimulation** and **cytokine** secretion, which ensures a robust T/ B cell response * Important field for development in order to improve responses to subunit vaccines * Novel adjuvants are toll-like receptor ligands eg CPG repeats
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_Adjuvants_ * Boost immune response to the antigen * Widely used, but mechanism understood only relatively recently * Eg alum, lipopolysaccharide * Work by binding to pattern-recognition receptors on antigen presenting cells * This enhances co-stimulation and cytokine secretion, which ensures a robust T/ B cell response * Important field for development in order to improve responses to ... vaccines * Novel adjuvants are ...-... receptor ligands eg CPG repeats
* Boost immune response to the antigen * Widely used, but mechanism understood only relatively recently * Eg alum, lipopolysaccharide * Work by binding to pattern-recognition receptors on antigen presenting cells * This enhances co-stimulation and cytokine secretion, which ensures a robust T/ B cell response * Important field for development in order to improve responses to **subunit** vaccines * Novel adjuvants are **toll-like** receptor ligands eg CPG repeats
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Novel adjuvants are ...-like receptor ligands eg CPG repeats
Novel adjuvants are **toll**-like receptor ligands eg CPG repeats
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How do Adjuvants work?
Work by binding to pattern-recognition receptors on antigen presenting cells
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Give an example of an adjuvant
alum
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_New approaches: mRNA vaccines_ * For mRNA vaccines, sequence generated which codes for critical pathogen antigens * Delivered via ... eg lipid nanoparticles OR ... vivo (harvest circulating monocytes then return to recipient) * Sequence translated by host cells to produce encoded antigens, which then stimulates host immune response * In development since ... * Key technical challenges * Preventing degradation of mRNA – solution was lipid nanoparticle delivery * Inflammatory response caused by mRNA – solution was modifying nucleosides * Potentially rapidly available and modifiable; relatively quick and easy to produce and adapt once facility established * Utilised in new SARS-CoV2 vaccines made by Pfizer and Moderna; mRNA codes for viral spike protein
* For mRNA vaccines, sequence generated which codes for critical pathogen antigens * Delivered via **vector** eg lipid nanoparticles OR **ex** vivo (harvest circulating monocytes then return to recipient) * Sequence translated by host cells to produce encoded antigens, which then stimulates host immune response * In development since **1990s** * Key technical challenges * Preventing degradation of mRNA – solution was lipid nanoparticle delivery * Inflammatory response caused by mRNA – solution was modifying nucleosides * Potentially rapidly available and modifiable; relatively quick and easy to produce and adapt once facility established * Utilised in new SARS-CoV2 vaccines made by Pfizer and Moderna; mRNA codes for viral spike protein
107
_New approaches: mRNA vaccines_ * For mRNA vaccines, ... generated which codes for critical ... antigens * Delivered via vector eg lipid nanoparticles OR ex vivo (harvest circulating monocytes then return to recipient) * Sequence translated by host cells to produce encoded antigens, which then stimulates host immune response * In development since 1990s * Key technical challenges * Preventing ... of mRNA – solution was lipid nanoparticle delivery * ... response caused by mRNA – solution was modifying nucleosides * Potentially rapidly available and modifiable; relatively quick and easy to produce and adapt once facility established * Utilised in new SARS-CoV2 vaccines made by Pfizer and Moderna; mRNA codes for viral spike protein
* For mRNA vaccines, **sequence** generated which codes for critical **pathogen** antigens * Delivered via vector eg lipid nanoparticles OR ex vivo (harvest circulating monocytes then return to recipient) * Sequence translated by host cells to produce encoded antigens, which then stimulates host immune response * In development since 1990s * Key technical challenges * Preventing **degradation** of mRNA – solution was lipid nanoparticle delivery * **Inflammatory** response caused by mRNA – solution was modifying nucleosides * Potentially rapidly available and modifiable; relatively quick and easy to produce and adapt once facility established * Utilised in new SARS-CoV2 vaccines made by Pfizer and Moderna; mRNA codes for viral spike protein
108
_New approaches: mRNA vaccines_ * For mRNA vaccines, sequence generated which codes for critical pathogen antigens * Delivered via vector eg lipid nanoparticles OR ex vivo (harvest circulating monocytes then return to recipient) * Sequence translated by host cells to produce encoded antigens, which then stimulates host immune response * In development since 1990s * Key technical challenges * Preventing degradation of mRNA – solution was lipid ... delivery * Inflammatory response caused by mRNA – solution was modifying nucleosides * Potentially rapidly available and modifiable; relatively quick and easy to produce and adapt once facility established * Utilised in new SARS-CoV2 vaccines made by ... and ...; mRNA codes for viral spike protein
* For mRNA vaccines, sequence generated which codes for critical pathogen antigens * Delivered via vector eg lipid nanoparticles OR ex vivo (harvest circulating monocytes then return to recipient) * Sequence translated by host cells to produce encoded antigens, which then stimulates host immune response * In development since 1990s * Key technical challenges * Preventing degradation of mRNA – solution was lipid **nanoparticle** delivery * Inflammatory response caused by mRNA – solution was modifying nucleosides * Potentially rapidly available and modifiable; relatively quick and easy to produce and adapt once facility established * Utilised in new SARS-CoV2 vaccines made by **Pfizer and Moderna**; mRNA codes for viral spike protein
109
mRNA Vaccine - How does it work?
110
_Novel approaches: viral vector_ * ... virus that can be easily grown in culture engineered to carry genes encoding ... antigens * Altered virus used as a live-attenuated vaccine or a non-replicating viral vaccine * Challenges * Pre-existing immunity to viral vector * Immune responses to viral vector may affect later use * ... SARS-CoV2 vaccine utilises replication-deficient Simian adenovirus carrying spike protein gene * Russian Sputnik V vaccine uses similar approach, but with two different replication-deficient human adenovirus vectors – one for priming, one for boosting * Johnson and Johnson product is another replication-deficient simian adenoviral vector; trialled to demonstrate single-dose protection
* **Benign** virus that can be easily grown in culture engineered to carry genes encoding **immunogenic** antigens * Altered virus used as a live-attenuated vaccine or a non-replicating viral vaccine * Challenges * Pre-existing immunity to viral vector * Immune responses to viral vector may affect later use * **Astra-Zenica** SARS-CoV2 vaccine utilises replication-deficient Simian adenovirus carrying spike protein gene * Russian Sputnik V vaccine uses similar approach, but with two different replication-deficient human adenovirus vectors – one for priming, one for boosting * Johnson and Johnson product is another replication-deficient simian adenoviral vector; trialled to demonstrate single-dose protection
111
_Novel approaches: viral vector_ * Benign virus that can be easily grown in culture engineered to carry genes encoding immunogenic antigens * Altered virus used as a live-attenuated vaccine or a non-replicating viral vaccine * Challenges * Pre-existing ... to viral vector * Immune responses to viral vector may affect ... use * Astra-Zenica SARS-CoV2 vaccine utilises replication-deficient Simian adenovirus carrying spike protein gene * Russian Sputnik V vaccine uses similar approach, but with two different replication-deficient human adenovirus vectors – one for priming, one for boosting * Johnson and Johnson product is another replication-deficient simian adenoviral vector; trialled to demonstrate single-dose protection
* Benign virus that can be easily grown in culture engineered to carry genes encoding immunogenic antigens * Altered virus used as a live-attenuated vaccine or a non-replicating viral vaccine * Challenges * Pre-existing **immunity** to viral vector * Immune responses to viral vector may affect **later** use * Astra-Zenica SARS-CoV2 vaccine utilises replication-deficient Simian adenovirus carrying spike protein gene * Russian Sputnik V vaccine uses similar approach, but with two different replication-deficient human adenovirus vectors – one for priming, one for boosting * Johnson and Johnson product is another replication-deficient simian adenoviral vector; trialled to demonstrate single-dose protection
112
_Novel approaches: viral vector_ * Benign virus that can be easily grown in culture engineered to carry genes encoding immunogenic antigens * Altered virus used as a live-attenuated vaccine or a non-replicating viral vaccine * Challenges * Pre-existing immunity to viral vector * Immune responses to viral vector may affect later use * Astra-Zenica SARS-CoV2 vaccine utilises replication-deficient Simian adenovirus carrying ... protein gene * Russian Sputnik V vaccine uses similar approach, but with two different replication-deficient human adenovirus vectors – one for ..., one for boosting * Johnson and Johnson product is another replication-deficient simian adenoviral vector; trialled to demonstrate ...-dose protection
* Benign virus that can be easily grown in culture engineered to carry genes encoding immunogenic antigens * Altered virus used as a live-attenuated vaccine or a non-replicating viral vaccine * Challenges * Pre-existing immunity to viral vector * Immune responses to viral vector may affect later use * Astra-Zenica SARS-CoV2 vaccine utilises replication-deficient Simian adenovirus carrying **spike** protein gene * Russian Sputnik V vaccine uses similar approach, but with two different replication-deficient human adenovirus vectors – one for **priming**, one for boosting * Johnson and Johnson product is another replication-deficient simian adenoviral vector; trialled to demonstrate **single**-dose protection
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Example of lenteviral vaccine transduction
114
Recombinant protein subunit vaccine examples (2)
Hep B and HPV
115
Hepatitis B is what type of vaccine?
Recombinant protein subunit vaccine
Year 2 Medicine
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