Vaccines Flashcards
Immunisation is an … process by which an individual is rendered …
Immunisation is an artificial process by which an individual is rendered immune
What is Immunisation?
Immunisation is an artificial process by which an individual is rendered immune
… immunisation – no immune response in recipient
Passive immunisation – no immune response in recipient
… immunisation (…) – recipient develops a protective adaptive immune response
Active immunisation (vaccination) – recipient develops a protective adaptive immune response
Passive vs Active Immunisation
- Passive immunisation – no immune response in recipient
- Active immunisation (vaccination) – recipient develops a protective adaptive immune response
Immunisation is one of the cheapest and most effective methods of improving … and reducing …
Immunisation is one of the cheapest and most effective methods of improving survival and reducing morbidity
Immunisation estimated reduction in mortality worldwide … million/ yr
Immunisation estimated reduction in mortality worldwide 3 million/ yr
Variola = … virus
Variola =smallpox virus
Variolation
- Variola = … virus
- For variolation, fluid harvested from pustules of … individuals and injected under skin of recipient
- Crude method of obtaining an ‘…’ vaccine
- Documented practice in Far East, Middle East and South Asia from 1000AD
- Limited use in UK (1700s)
- Variola =smallpox virus
- For variolation, fluid harvested from pustules of recovering individuals and injected under skin of recipient
- Crude method of obtaining an ‘inactivated’ vaccine
- Documented practice in Far East, Middle East and South Asia from 1000AD
- Limited use in UK (1700s)
Jenner
- Used fluid from … lesions to protect against … infection in 1796; recipient was James Phipps, aged 8
- Subsequently experimented with several other children, including his own infant son; published findings in 1798
- The first documented use of a live-attenuated vaccine and the birth of modern immunisation
- Used fluid from cowpox lesions to protect against smallpox infection in 1796; recipient was James Phipps, aged 8
- Subsequently experimented with several other children, including his own infant son; published findings in 1798
- The first documented use of a live-attenuated vaccine and the birth of modern immunisation
- Jenner used fluid from cowpox lesions to protect against … infection in 1796; recipient was James Phipps, aged 8
- Subsequently experimented with several other children, including his own infant son; published findings in 1798
- The first documented use of a …-attenuated vaccine and the birth of … immunisation
- Jenner used fluid from cowpox lesions to protect against … infection in 1796; recipient was James Phipps, aged 8
- Subsequently experimented with several other children, including his own infant son; published findings in 1798
- The first documented use of a live-attenuated vaccine and the birth of modern immunisation
Passive immunisation
- Immunity conferred without an … host response on behalf of recipient
- Passive vaccines are preparations of … taken from hyper-immune donors, either human or animal
- Examples:
- Immunoglobulin replacement in antibody deficiency
- VZV prophylaxis eg during exposure during …
- Anti-toxin therapies eg … anti-serum
- Protection is temporary
- Immunity conferred without an active host response on behalf of recipient
- Passive vaccines are preparations of antibodies taken from hyper-immune donors, either human or animal
- Examples:
- Immunoglobulin replacement in antibody deficiency
- VZV prophylaxis eg during exposure during pregnancy
- Anti-toxin therapies eg snake anti-serum
- Protection is temporary
Passive immunisation
- Immunity conferred without an active host response on behalf of recipient
- Passive vaccines are preparations of antibodies taken from …-immune donors, either human or animal
- Examples:
- Immunoglobulin replacement in antibody deficiency
- VZV prophylaxis eg during exposure during pregnancy
- Anti-toxin therapies eg snake anti-serum
- Protection is …
- Immunity conferred without an active host response on behalf of recipient
- Passive vaccines are preparations of antibodies taken from hyper-immune donors, either human or animal
- Examples:
- Immunoglobulin replacement in antibody deficiency
- VZV prophylaxis eg during exposure during pregnancy
- Anti-toxin therapies eg snake anti-serum
- Protection is temporary
Is passive immunisation protection permanent or temporary?
temporary
VZV exposure during pregnancy
- VZV causes …
- If they have had …, no need to do anything
- If no history or unsure - blood test to check for VZV IgG - if positive, reassure (has memory response - immune to …) If negative or equivocal, give VZV immunoglobulin to protect against infection
- VZV during pregnancy can cause fetal complications.
- In case of exposure, women should contact their GP, Midwife or Virology Dept. Urgent VZV serology is available when required
- VZV causes chickenpox
- If they have had chickenpox, no need to do anything
- If no history or unsure - blood test to check for VZV IgG - if positive, reassure (has memory response - immune to chickenpox) If negative or equivocal, give VZV immunoglobulin to protect against infection
- VZV during pregnancy can cause fetal complications.
- In case of exposure, women should contact their GP, Midwife or Virology Dept. Urgent VZV serology is available when required
VZV exposure during pregnancy
- VZV causes chickenpox
- If they have had chickenpox, no need to do anything
- If no history or unsure - blood test to check for VZV IgG - if …, reassure (has memory response - immune to chickenpox) If … or …, give VZV immunoglobulin to protect against infection
- VZV during pregnancy can cause fetal complications.
- In case of exposure, women should contact their GP, Midwife or Virology Dept. Urgent VZV serology is available when required
- VZV causes chickenpox
- If they have had chickenpox, no need to do anything
- If no history or unsure - blood test to check for VZV IgG - if positive, reassure (has memory response - immune to chickenpox) If negative or equivocal, give VZV immunoglobulin to protect against infection
- VZV during pregnancy can cause fetal complications.
- In case of exposure, women should contact their GP, Midwife or Virology Dept. Urgent VZV serology is available when required
VZV exposure during pregnancy
- VZV causes chickenpox
- If they have had chickenpox, no need to do anything
- If no history or unsure - blood test to check for VZV IgG - if positive, reassure (has memory response - immune to chickenpox) If negative or equivocal, give VZV immunoglobulin to protect against infection
- VZV during pregnancy can cause … …
- In case of exposure, women should contact their GP, Midwife or Virology Dept. Urgent VZV serology is available when required
- VZV causes chickenpox
- If they have had chickenpox, no need to do anything
- If no history or unsure - blood test to check for VZV IgG - if positive, reassure (has memory response - immune to chickenpox) If negative or equivocal, give VZV immunoglobulin to protect against infection
- VZV during pregnancy can cause fetal complications.
- In case of exposure, women should contact their GP, Midwife or Virology Dept. Urgent VZV serology is available when required
VZV exposure during pregnancy
- VZV causes chickenpox
- If they have had chickenpox, what is done?
- If no history or unsure - blood test to check for VZV … - if positive, reassure (has memory response - immune to chickenpox) If negative or equivocal, give VZV immunoglobulin to protect against infection
- VZV during pregnancy can cause fetal complications.
- In case of exposure, women should contact their GP, Midwife or Virology Dept. Urgent VZV serology is available when required
- VZV causes chickenpox
- If they have had chickenpox, no need to do anything
- If no history or unsure - blood test to check for VZV IgG - if positive, reassure (has memory response - immune to chickenpox) If negative or equivocal, give VZV immunoglobulin to protect against infection
- VZV during pregnancy can cause fetal complications.
- In case of exposure, women should contact their GP, Midwife or Virology Dept. Urgent VZV serology is available when required
In pregnant women with no history of chickenpox or unsure, do bloods to check for VZV IgG - If positive, what does that mean?
Reassure - they are immune, if negative this means they have not had chickenpox before and give VZV immunoglobulin
Active immunisation (vaccination)
- Immunity conferred in recipient following the generation of an … immune response
- General principle is to stimulate an … immune response without causing …-… infection
- Immunity conferred in recipient following the generation of an adaptive immune response
- General principle is to stimulate an adaptive immune response without causing clinically-apparent infection
Active immunisation is the same as …
Active immunisation (vaccination)
General principles of Vaccination (1)
- To be effective, vaccines need to be administered to targeted … in advance of … to the pathogen of interest
- Vaccination of sufficient numbers impacts the transmission dynamic so that even unimmunised individuals are at … risk – called … …
- As vaccines are given to … individuals, the risk-to-benefit ratio requires that vaccines meet high safety standards
- To be effective, vaccines need to be administered to targeted cohorts in advance of exposure to the pathogen of interest
- Vaccination of sufficient numbers impacts the transmission dynamic so that even unimmunised individuals are at low risk – called herd immunity
- As vaccines are given to healthy individuals, the risk-to-benefit ratio requires that vaccines meet high safety standards
General principles of Vaccination (2)
- Most vaccines work by generating a long-lasting, high-affinity I… antibody response
- These antibodies are sufficient to prevent primary infection
- A strong … T cell response is a pre-requisite for this
- The most effective vaccines are for diseases where natural exposure results in protective immunity
- ‘Problem’ diseases are generally those where the immune system cannot eliminate infection or generate …-… protective immunity during natural infection
- Eg MTB, HIV, malaria
- Most vaccines work by generating a long-lasting, high-affinity IgG antibody response
- These antibodies are sufficient to prevent primary infection
- A strong CD4 T cell response is a pre-requisite for this
- The most effective vaccines are for diseases where natural exposure results in protective immunity
- ‘Problem’ diseases are generally those where the immune system cannot eliminate infection or generate long-lasting protective immunity during natural infection
- Eg MTB, HIV, malaria
General principles of Vaccination (2)
- Most vaccines work by generating a long-lasting, …-affinity IgG antibody response
- These antibodies are sufficient to prevent … infection
- A strong CD4 T cell response is a pre-requisite for this
- The most effective vaccines are for diseases where natural exposure results in protective immunity
- ‘…’ diseases are generally those where the immune system cannot eliminate infection or generate long-lasting protective immunity during natural infection
- Eg MTB, HIV, malaria
- Most vaccines work by generating a long-lasting, high-affinity IgG antibody response
- These antibodies are sufficient to prevent primary infection
- A strong CD4 T cell response is a pre-requisite for this
- The most effective vaccines are for diseases where natural exposure results in protective immunity
- ‘Problem’ diseases are generally those where the immune system cannot eliminate infection or generate long-lasting protective immunity during natural infection
- Eg MTB, HIV, malaria
What goes into a vaccine?
- …
- To stimulate an …-specific T and B cell response
- …
- Immune potentiators to increase the immunogenicity of the vaccine
- ‘Excipients’
- Various diluents and additives required for vaccine integrity
-
Antigen
- To stimulate an antigen-specific T and B cell response
-
Adjuvants
- Immune potentiators to increase the immunogenicity of the vaccine
- ‘Excipients’
- Various diluents and additives required for vaccine integrity
What goes into a vaccine?
- Antigen
- To … an antigen-specific T and B cell response
- Adjuvants
- Immune potentiators to increase the immunogenicity of the vaccine
- ‘…’
- Various diluents and additives required for vaccine integrity
- Antigen
- To stimulate an antigen-specific T and B cell response
- Adjuvants
- Immune potentiators to increase the immunogenicity of the vaccine
- ‘Excipients’
- Various diluents and additives required for vaccine integrity
Classification of active vaccines on the basis of the antigen
- Active Vaccines - divided into … organism or subunit
- … organism
- Live-attenuated vaccine
- Inactivated (killed)
- S..
- Toxoids
- Capsular polysaccharide
- Conjugated polysaccharide
- Recombinant subunit
- ?mRNA, VLPs, viral vector
- Active Vaccines - divided into whole organism or subunit
-
Whole organism
- Live-attenuated vaccine
- Inactivated (killed)
-
Subunit
- Toxoids
- Capsular polysaccharide
- Conjugated polysaccharide
- Recombinant subunit
- ?mRNA, VLPs, viral vector
Classification of active vaccines on the basis of the antigen
- Active Vaccines - divided into whole organism or subunit
- Whole organism
- …-… vaccine
- Inactivated (killed)
- Subunit
- T…
- Capsular polysaccharide
- Conjugated polysaccharide
- Recombinant subunit
- ?mRNA, VLPs, viral vector
- Active Vaccines - divided into whole organism or subunit
- Whole organism
- Live-attenuated vaccine
- Inactivated (killed)
- Subunit
- Toxoids
- Capsular polysaccharide
- Conjugated polysaccharide
- Recombinant subunit
- ?mRNA, VLPs, viral vector
Classification of active vaccines on the basis of the antigen
- Active Vaccines - divided into whole organism or subunit
- Whole organism
- Live-attenuated vaccine
- … (killed)
- Subunit
- Toxoids
- C.. polysaccharide
- C… polysaccharide
- Recombinant subunit
- ?mRNA, VLPs, viral vector
- Active Vaccines - divided into whole organism or subunit
- Whole organism
- Live-attenuated vaccine
- Inactivated (killed)
- Subunit
- Toxoids
- Capsular polysaccharide
- Conjugated polysaccharide
- Recombinant subunit
- ?mRNA, VLPs, viral vector
Classification of active vaccines on the basis of the antigen
- Active Vaccines - divided into whole organism or subunit
- Whole organism
- Live-attenuated vaccine
- Inactivated (killed)
- Subunit
- Toxoids
- Capsular polysaccharide
- Conjugated polysaccharide
- … subunit
- ?..RNA, VLPs, viral …
- Active Vaccines - divided into whole organism or subunit
- Whole organism
- Live-attenuated vaccine
- Inactivated (killed)
- Subunit
- Toxoids
- Capsular polysaccharide
- Conjugated polysaccharide
- Recombinant subunit
- ?mRNA, VLPs, viral vector
Live-attenuated vaccines
- Live but attenuated organisms used
- Prolonged culture … vivo in non-… conditions
- This selects variants that are adapted to live in …
- These variants are viable in vivo but are no longer able to cause disease
- Live but attenuated organisms used
- Prolonged culture ex vivo in non-physiological conditions
- This selects variants that are adapted to live in culture
- These variants are viable in vivo but are no longer able to cause disease
Live-attenuated vaccines
- Live but attenuated organisms used
- Prolonged culture ex vivo in non-physiological conditions
- This selects variants that are adapted to live in culture
- These variants are viable … vivo but are no longer able to cause …
- Live but attenuated organisms used
- Prolonged culture ex vivo in non-physiological conditions
- This selects variants that are adapted to live in culture
- These variants are viable in vivo but are no longer able to cause disease
Examples of Live-attenuated vaccines
- M…
- M…
- R…
- P… (Sabin)
- B…
- Cholera
- Zoster
- VZV (not routinely used for primary prevention in UK at present)
- Live influenza (not main product in UK at present)
- Measles
- Mumps
- Rubella
- Polio (Sabin)
- BCG
- Cholera
- Zoster
- VZV (not routinely used for primary prevention in UK at present)
- Live influenza (not main product in UK at present)
Pros and cons of live vaccines
- Replication … …, therefore produces highly effective and durable responses
- In case of viral vaccine, intracellular infection leads to good … response
- Repeated … not required
- In some diseases, may get secondary protection of unvaccinated individuals, who are infected with the live-attenuated vaccine strain eg polio
- Storage problems, short shelf-life
- May revert to wild type Eg vaccine associated poliomyelitis: around 1 in 750 000 recipients
- Immunocompromised recipients may develop clinical disease
- Replication within host, therefore produces highly effective and durable responses
- In case of viral vaccine, intracellular infection leads to good CD8 response
- Repeated boosting not required
- In some diseases, may get secondary protection of unvaccinated individuals, who are infected with the live-attenuated vaccine strain eg polio
- Storage problems, short shelf-life
- May revert to wild type Eg vaccine associated poliomyelitis: around 1 in 750 000 recipients
- Immunocompromised recipients may develop clinical disease
Pros and cons of live vaccines
- Replication within host, therefore produces highly effective and durable responses
- In case of viral vaccine, intracellular infection leads to good CD8 response
- Repeated boosting not required
- In some diseases, may get … protection of … individuals, who are infected with the live-attenuated vaccine strain eg polio
- … problems, short …-life
- May revert to wild type Eg vaccine associated poliomyelitis: around 1 in 750 000 recipients
- Immunocompromised recipients may develop clinical disease
- Replication within host, therefore produces highly effective and durable responses
- In case of viral vaccine, intracellular infection leads to good CD8 response
- Repeated boosting not required
- In some diseases, may get secondary protection of unvaccinated individuals, who are infected with the live-attenuated vaccine strain eg polio
- Storage problems, short shelf-life
- May revert to wild type Eg vaccine associated poliomyelitis: around 1 in 750 000 recipients
- Immunocompromised recipients may develop clinical disease
Pros and cons of live vaccines
- Replication within host, therefore produces highly effective and durable responses
- In case of viral vaccine, intracellular infection leads to good CD8 response
- Repeated boosting not required
- In some diseases, may get secondary protection of unvaccinated individuals, who are infected with the live-attenuated vaccine strain eg polio
- Storage problems, short shelf-life
- May revert to … type Eg vaccine associated poliomyelitis: around 1 in 750 000 recipients
- … recipients may develop clinical disease
- Replication within host, therefore produces highly effective and durable responses
- In case of viral vaccine, intracellular infection leads to good CD8 response
- Repeated boosting not required
- In some diseases, may get secondary protection of unvaccinated individuals, who are infected with the live-attenuated vaccine strain eg polio
- Storage problems, short shelf-life
- May revert to wild type Eg vaccine associated poliomyelitis: around 1 in 750 000 recipients
- Immunocompromised recipients may develop clinical disease
Varicella-Zoster Vaccine
- Primary infection = …
- Cellular and humoral immunity provide lifelong protection, but viruses establishes permanent infection of sensory ganglia
- Viral reactivation= …
- Particularly elderly, fairly debilitating and may cause long-term neuropathic pain
- Primary infection = chickenpox
- Cellular and humoral immunity provide lifelong protection, but viruses establishes permanent infection of sensory ganglia
- Viral reactivation= zoster (shingles)
- Particularly elderly, fairly debilitating and may cause long-term neuropathic pain
Varicella-Zoster Vaccine
- Primary infection = chickenpox
- Cellular and humoral immunity provide … protection, but viruses establishes … infection of sensory ganglia
- Viral … = zoster (shingles)
- Particularly elderly, fairly debilitating and may cause long-term neuropathic pain
- Primary infection = chickenpox
- Cellular and humoral immunity provide lifelong protection, but viruses establishes permanent infection of sensory ganglia
- Viral reactivation=zoster (shingles)
- Particularly elderly, fairly debilitating and may cause long-term neuropathic pain
Varicella-Zoster Vaccine
- Primary infection = …
- Cellular and humoral immunity provide lifelong protection, but viruses establishes permanent infection of sensory ganglia
- Viral reactivation= Zoster (shingles)
- Particularly …, fairly … and may cause long-term … pain
- Primary infection = chickenpox
- Cellular and humoral immunity provide lifelong protection, but viruses establishes permanent infection of sensory ganglia
- Viral reactivation= zoster (shingles)
- Particularly elderly, fairly debilitating and may cause long-term neuropathic pain
Varicella-Zoster Vaccine
- …-… VZV, works by induction of anti-VZV antibodies
- …% effective at preventing chickenpox
- Attenuated virus does establish infection of sensory ganglia, but subsequent zoster is probably rare
- ..-..% mild post-vaccination varicella infection
- Not on UK schedule at present, because:
- VZV is a fairly benign childhood infection
- ?Schedule is already crowded and controversial
- Safety concerns based on evidence from other countries
- ‘Disease shift’ to unvaccinated adults, in whom VZV is less well tolerated
- Increase in zoster – probably reduced immune boosting in adults
- Live-attenuated VZV, works by induction of anti-VZV antibodies
- 95% effective at preventing chickenpox
- Attenuated virus does establish infection of sensory ganglia, but subsequent zoster is probably rare
- 3-5% mild post-vaccination varicella infection
- Not on UK schedule at present, because:
- VZV is a fairly benign childhood infection
- ?Schedule is already crowded and controversial
- Safety concerns based on evidence from other countries
- ‘Disease shift’ to unvaccinated adults, in whom VZV is less well tolerated
- Increase in zoster – probably reduced immune boosting in adults
Varicella-Zoster Vaccine
- Live-attenuated VZV, works by induction of anti-VZV antibodies
- 95% effective at preventing chickenpox
- Attenuated virus does establish infection of sensory …, but subsequent zoster is probably rare
- 3-5% mild post-vaccination varicella infection
- Not on UK schedule at present, because:
- VZV is a fairly … childhood infection
- ?Schedule is already crowded and c…
- … concerns based on evidence from other countries
- ‘Disease shift’ to unvaccinated adults, in whom VZV is less well tolerated
- Increase in zoster – probably reduced immune boosting in adults
- Live-attenuated VZV, works by induction of anti-VZV antibodies
- 95% effective at preventing chickenpox
- Attenuated virus does establish infection of sensory ganglia, but subsequent zoster is probably rare
- 3-5% mild post-vaccination varicella infection
- Not on UK schedule at present, because:
- VZV is a fairly benign childhood infection
- ?Schedule is already crowded and controversial
-
Safety concerns based on evidence from other countries
- ‘Disease shift’ to unvaccinated adults, in whom VZV is less well tolerated
- Increase in zoster – probably reduced immune boosting in adults
Varicella-Zoster Vaccine
- Live-attenuated VZV, works by induction of anti-VZV antibodies
- 95% effective at preventing chickenpox
- Attenuated virus does establish infection of sensory ganglia, but subsequent zoster is probably rare
- 3-5% mild post-vaccination varicella infection
- Not on UK schedule at present, because:
- VZV is a fairly benign childhood infection
- ?Schedule is already crowded and controversial
- Safety concerns based on evidence from other countries
- ‘… shift’ to unvaccinated adults, in whom VZV is less well tolerated
- Increase in … – probably reduced immune boosting in adults
- Live-attenuated VZV, works by induction of anti-VZV antibodies
- 95% effective at preventing chickenpox
- Attenuated virus does establish infection of sensory ganglia, but subsequent zoster is probably rare
- 3-5% mild post-vaccination varicella infection
- Not on UK schedule at present, because:
- VZV is a fairly benign childhood infection
- ?Schedule is already crowded and controversial
- Safety concerns based on evidence from other countries
- ‘Disease shift’ to unvaccinated adults, in whom VZV is less well tolerated
- Increase in zoster – probably reduced immune boosting in adults
The varicella-zoster vaccine is …% effective at preventing chickenpox
95% effective at preventing chickenpox
Is VZV (Varicella-Zoster vaccine) on UK vaccination schedule?
- Not on UK schedule at present, because:
- VZV is a fairly benign childhood infection
- ?Schedule is already crowded and controversial
- Safety concerns based on evidence from other countries
- ‘Disease shift’ to unvaccinated adults, in whom VZV is less well tolerated
- Increase in zoster – probably reduced immune boosting in adults
Zoster, immunity and aging
- The incidence of zoster … with age, in parallel with … cell-mediated immune responses to zoster
- The incidence of zoster increases with age, in parallel with declining cell-mediated immune responses to zoster
Zoster vaccination
- Similar VZV preparation to that used for … disease, but much … dose
- Aims to boost memory T cell responses to VZV
- In over 60s, 50% reduction in zoster incidence after vaccination compared to controls; reduced severity and complications amongst vaccinated cases
- Similar VZV preparation to that used for primary disease, but much higher dose
- Aims to boost memory T cell responses to VZV
- In over 60s, 50% reduction in zoster incidence after vaccination compared to controls; reduced severity and complications amongst vaccinated cases