15 - Vaccines Flashcards

1
Q

Immune memory:

A

-1st exposure (ex. vaccination)
-2nd exposure: anamnestic immune response (MEMORY)

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2
Q

Vaccine induced immunity:

A
  1. Vaccination
  2. Onset
  3. Duration of immunity
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3
Q

Booster immunizations:

A

-give a vaccine before the primary vaccination response has dropped
>get another response and extend protection

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4
Q

Vaccination origins:

A

-Edward Jenner with cowpox and smallpox
-China in 200BC: pictures to show inoculation and vaccination for prevention and treatment of disease

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5
Q

Vaccines do work:

A

-have saved more Canadian lives than any other health intervention in the last 50 years
Ex. polio and diphtheria are 100% gone

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6
Q

Vaccine administration routes:

A

-injection
-oral
-intranasal
-skin patch?
-oral?

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7
Q

Economic value of vaccination in livestock:

A

*most effective means of preventing infectious diseases
-cost effective in long term by increasing health status

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8
Q

How does vaccination have long term effectiveness with health status in livestock?

A

-avoids use of antibiotics
-decreases mortality
-improves health status
-better feed conversion
-better carcass weight

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9
Q

The ideal vaccine:

A

-fast onset and long duration of immunity
-single immunization
-highly effective (prophylactic and therapeutic)
-efficacious in all age groups (including niche populations)
-safe, no side effects
-cost effective
-easy to store, transport and administer
-DIVA vaccine

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10
Q

prophylactic and therapeutic:

A

-prophylactic: healthy animals that are not sick yet
-therapeutic: animals that already have the disease

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11
Q

DIVA vaccine:

A

-Differentiate Infected from Vaccinate Animals
>want to be able to prove that the animal never got the disease and it was just vaccinated
*want to prove that it is disease free
Ex. FMD, tuberculosis

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12
Q

What is a vaccine?

A

-a substance given to stimulate a primary immune response
>prepares the body for contact with the actual disease or illness
*now can mount a secondary immune response

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13
Q

Secondary immune response:

A

-better fight
-avoid serious disease

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14
Q

Vaccine components:

A
  1. Antigen
  2. Adjuvants
  3. Diluents, stabilizers, preservatives, trace components
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15
Q

Antigen: vaccine component

A

-foreign material
-subunit, inactivated, or attenuated
-single or multiple antigens (multivalent)

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16
Q

Adjuvants: vaccine component

A

-enhance immune response
-modulate the type of immunity (intracellular vs extracellular)
-shorten onset and extend duration of immunity
Ex. oil-in water, TLR, combination adjuvants, etc

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17
Q

3 main approaches to making a vaccine:

A
  1. Whole pathogen
  2. Parts
  3. Genetic material (DNA or RNA)
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18
Q

RSV F protein:

A

-RSV particle with various structures on surface
-various targets for antibody
>certain ones have better neutralizing effects

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19
Q

Whole vaccine types:

A

-live-attenuated
-inactivated (killed)

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20
Q

Live-attenuated vaccine pathway:

A
  1. Vaccine enters cell and gets translated
  2. Some proteins end up in PM (NK cells) and others on MHCI (CTLs)
  3. Dead cells is phagocytosed by APC, presents it on MHCII (T helper cell, and B cell activation)
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21
Q

Live-attenuated vaccines:

A

-live pathogen
-grown in cell-culture
-replicates
-brings lots of danger-signal
*attenuated: doesn’t cause disease

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22
Q

Live attenuated vaccines immune response:

A

-very effective (viruses: intracellular)
-long-lasting, rapid onset
-strong Ab response
-strong T cell response (cytotoxic)

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23
Q

Advantage of live-attenuated vaccines:

A

*best immune response (gold standard)
-long lasting and very effective (cytotoxic and humoral)

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24
Q

Disadvantage of live-attenuated vaccines:

A

-shedding of vaccine virus into environment
-safety concern: can revert to FULL virulence
-not recommend during gestation or in immune compromised

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25
Q

Endogenous pathway:

A

-vaccine goes into cell and ends up on MHC I
>presented to CTLs

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26
Q

Exogenous pathway:

A

-extracellular pathogen taken up into phagosome inside cell
-antigen presentation on MHC II to T helper cells

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27
Q

Cross presentation:

A

-some antigen entering through exogenous pathway is also processed via endogenous pathway
*exogenous antigen is loaded onto MHCI
*very small portion (maybe 5-8%)

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28
Q

Inactivated cell vaccine steps:

A
  1. Does NOT enter cell
  2. Phagocytosed by APC and displayed on MHCII for CD4+ T cells and get B cell activation
    *humoral response
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29
Q

Inactivated (killed) vaccines:

A

-dead, cannot cause disease
-grown in cell culture and inactivated
-pathogen can not replicate
-often requires additional adjuvants
Ex. use this in pregnant animals

30
Q

Inactivated vaccine immune response:

A

-extracellular antigen
-not as strong, short-lived
-strong antibody response
-weak T cell response (cytotoxic)

31
Q

Inactivated vaccine requires adjuvants:

A

-enhance immune response
-provide “danger signal”
>trick the cell and get more cross presentation/think it is intracellular

32
Q

Inactivated vaccine advantages:

A

-very safe, no reversion to virulence
-no shedding into environment
-can NOT cause disease

33
Q

Part vaccine types:

A

-recombinant (subunit) vaccines
-vectored vaccines

34
Q

Recombinant (subunit) vaccines:

A

-only part of a pathogen
-can be expressed in various expression systems or mechanically obtained (split vaccines)
-often cheaper

35
Q

Subunit types:

A
  1. Split
  2. Recombinant
36
Q

Split vaccine (subunit):

A

-directly purified from mechanically DISRUPTED pathogen

37
Q

Recombinant vaccine (subunit):

A

-expressed in bacteria, mammalian cells, plants and baculovirus and then purified
-only part of pathogen
-can not replicate itself
-not very immunogenic, requires adjuvant

38
Q

Recombinant subunit vaccine immune response:

A

-not as strong, short-lived
-strong antibody response
-weak T-cell response (cytotoxic)

39
Q

Recombinant subunit vaccines adjuvants:

A

-enhance immune response
-provide ‘danger ‘signal’

40
Q

Recombinant subunit vaccine advantages:

A

-very safe, no live pathogen involved
-no shedding into environment
-cost effective

41
Q

Subunit vaccine steps:

A

-similar to inactivated

42
Q

Vectored vaccines:

A

-viral, bacterial and even parasite vectors
-live pathogen
-depends on target disease
-loading capacity, vector tropism, platforms, etc.
-vector itself does NOT cause disease

43
Q

Viral vectors:

A

-goal is to deliver subunit via vector
>vector gets into cell (intracellular)=*STIMULATES both antibody and cytotoxic T cell responses

44
Q

Viral vector delivery examples:

A

-Hemagglutinin (H1, H3)
-Neuraminidase (N1, N2)

45
Q

Viral vector steps:

A
  1. Viral vector enters cell (vector and target protein)
  2. Expression of viral and vector proteins
    >Some on MHCI (CTLs) others into PM (NK cell ADCC)
  3. Cell death: phagocytosis by APC (MHCII: T-cell and B cell for both target and vector)
46
Q

Vectored vaccines immune response:

A

-very effective (intracellular)
-long-lasting, rapid onset
-strong antibody response
-strong T cell response (cytotoxic)

47
Q

Vectored vaccine advantage:

A

-safety: can NOT revert back to full virulence

48
Q

Vectored vaccine disadvantage:

A

-shedding
-immunity against vector prevent multiple booster immunizations
>can overcome that (ex. Canarypox, very little immunity against it)

49
Q

How do you get viral vector vaccines:

A

-adenovirus: vector
-use molecular techniques to put subunits (Ex. influenza subunits)
-recombinant adenovirus: vector expressing influenza subunits)

50
Q

DNA/RNA vaccine steps:

A
  1. Endocytosis: inside a lipid coat
  2. Transcription/translation
  3. Protein expression
  4. MHC I (CTLs) and PM (NK cell ADCC)
  5. Cell death and some protein released: phagocytosed by APC
  6. MHC II (T-helper cell and B cell activation)
51
Q

Genetic material vaccine types:

A

-DNA and RNA vaccines
>DNA plasmids, mRNA, self-amplifying RNA (replicons)
>requires carriers for delivery (lipid carriers, nanoparticles, etc.)

52
Q

DNA/RNA vaccine:

A

-nucleic acid encoding for one protein
>taken up by cell and translated into protein (intracellular pathogen)
-can NOT replicate; can NOT cause disease

53
Q

DNA/RNA vaccine immune response:

A

-effective (intracellular)
-long-lasting, rapid onset
-good antibody response
-good T cell response (cytotoxicity)

54
Q

DNA/RNA vaccine advantages:

A

-safety: no live pathogen involved
-immunity: stimulates both cellular and humoral immunity
-can make them quickly

55
Q

DNA/RNA vaccine disadvantage:

A

-delivery is complicated, requires carriers (ex. liposomes) and/or nanoparticles
>solution: self-amplifying RNA (replicons) (can make their own copies)

56
Q

Sequivity platform:

A

-Merck will collect pathogens from your farm and sequence the genes
-then insert into RNA particles and create a vaccine
*always look at IFN-gamma response (need that for a good vaccine)

57
Q

Adjuvants: mechanisms of action

A
  1. Delivery of the vaccine: provide a depot effect
  2. Targeting of specific cells
  3. Stimulation of innate AND acquired immunity
58
Q

Delivery of vaccine: provide a depot effect (adjuvants)

A

-slow-release of antigen
-keep antigen at site of injection

59
Q

Targeting specific cells (adjuvants):

A

-targeting of APCs
-targeting of special tissues, uptake via mucosal surfaces

60
Q

Stimulation of innate and acquired immunity:

A

-provide ‘danger signal’
-recruitment and activation of immune cells (APCs)

61
Q

Different types of nano-adjuvants:

A

*many
-liposome
-PL nano-assembly
-oil in water

62
Q

Oil-in-water emulsion-based adjuvant:

A

-common ingredient: squalene (oil phase)
>bring all the cells together

63
Q

Montanide: adjuvant for swine vaccine:

A

-common
-mix with molecules that mimic danger signals
*enhances the update of vaccine by APCs

64
Q

Adjuvants in human medicine:

A

-aluminum
>strong Th2 response
>currently used for many viruses, so not getting as good of a response as we could get
-CpG 1018: more of a Th1 response
*more new ones coming

65
Q

How do DIVA vaccines work?

A

-allows us to differentiate infected from vaccinated animals
-vaccine has a ‘marker’
-use companion (serological) assay to determine if animal has antibodies to the marker protein

66
Q

DIVA vaccine has a ‘marker’:

A

-usually a deletion of on protein
>if has antibodies for green triangle and not the red marker protein=vaccinated
>if antibodies for green triangle and red marker protein=infected
-could be adding but then it is hard to say if they haven’t been infected

67
Q

Spread of a disease depends on:

A

-transmission rate of the pathogen within a susceptible population
*basic reproductive rate (average number of new cases caused by a individual case)

68
Q

Herd immunity:

A

-helps reduce the spread within the susceptible population
-higher the R0, the higher herd immunity threshold (HIT) needs to be
*protect vulnerable members of the population

69
Q

Regulatory approval of vaccines:

A

-CFIA-Canadian Centre for Veterinary Biologics
-USDA-Center for Veterinary biologics

70
Q

Do vaccines work? Examples

A

*Eradicated: small pox and Rinderpest
-Spanish flu
-polio
*saved millions of lives