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CBI - UOE > Vaccines > Flashcards

Vaccines Flashcards

1
Q

developing a vaccine is not

A

simple, cheap or quick

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2
Q

how long does it take create a vaccine and get it on the market

A

10/20 yr cycle

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3
Q

how much does a vaccine cost to develop

A

1 billion pounds

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4
Q

how many lives a year do vaccines save

A

2.5 million

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5
Q

how could an additional 2 million lives/yr be saved

A

by extending vaccine programs to all countries

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6
Q

infectious diseases are

A

one of the largest causes of mortality worldwide- save morbidity and mortality

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7
Q

there have been few events which have

A

made us think about cost-benefit analysis

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8
Q

why do some distrust vaccine e.g.

A

Do vaccines cause autism?
o Study reported by Andrew Wakefield in the Lancet 1998
o Severe trust of MMR
o People stopped immunizing their children- increase in infectious disease

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9
Q

why wasn’t Wakefield’s research valid

A

No controls included, autism would occur in 25 non-immunised children/month based on probability. No experimental evidence for the hypothesis that MMR peptides wee translocated in the brain.

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10
Q

why was wakefield so harmful

A

due to his research decreasing trust in vaccines and therefor limiting their uptake- reducing herd immunity

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11
Q

risk-benefit analysis

A

Shows how the morbidities related to the actual disease are ten times worse than the possible side effects of the reaction to the vaccine

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12
Q

compared to the actual disease itself

A

the possible and rare side-effects of vaccines are minute

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13
Q

main types of vaccines

A

live vaccines, killed vaccines, subunit vaccine sand DNA vaccines

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14
Q

Live vaccines e.g.

A

yellow fever

- in practice can cause disease in immunocompromised patients

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15
Q

what is preferred to a live vaccine

A

subunit vaccines- a way to reduce probability of side-effects

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16
Q

killed vaccines (attenuated)

A

by heating or exposure to chemicals

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17
Q

subunit vaccines

A

fragments of microorganisms e.g. proteins and polysaccharides

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18
Q

Naked DNA vaccines

A

the purest form - DNA makes proteins after injection using apparatus of the cell

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19
Q

example of a vaccine which had a side affect

A

H1N1 bird flu vaccine made people develop narcolepsy

- 800 European children developed narcolepsy after receiving H1N1 vaccine

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20
Q

more likely to make the US Olympic team

A

than suffer a severe allergic reaction

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21
Q

some people will develop

A

pain and swelling- but goes within a few days

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22
Q

sub-unit vaccines use

A

isolated components of microorganisms- protein or polysaccharide
- in reality only one or two of these components will work as an effective vaccine

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23
Q

immunity induced by sub-unit vaccines is almost always

A

triggering of antibodies

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24
Q

protective mechanism of binding antibodies to antigen

A
  • agglutination
  • opsonisation
  • neutralisation
  • activation of complement
  • inflammation
  • antibody-dependent cell-mediated cytotoxicity
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25
Q

agglutination

A

enhances phagocytosis and reduces the number of infectious units to be dealt with

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26
Q

opsonization

A

coating antigen with antibody enhances phagocytosis

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27
Q

neutralisation

A

blocks adhesion of bacteria and virus to mucosa and blocks active site of toxin

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28
Q

activation of complement

A

attaches complement to bacteria causing cell lysis

29
Q

inflammation

A

disruption of cell by complement/reactive protein attracts phagocytic and other defensive immune system cells

30
Q

Antibody-dependent cell mediated cytotoxicity

A

antibodies attached to target cell cause destruction by non-specific immune system cells

31
Q

example of a single subunit vaccine

A

diptheria

32
Q

Corynebacterium diptheria causes pathogenesis by releasing

A

a potent toxin

33
Q

diptheria potent toxin

A

blocks protein synthesis and causes heart failure

34
Q

since the diptheria vaccine was introduced om 1942

A

very few deaths

35
Q

how are vaccines prepared form diptheira toxin treated?

A

with formaldehyde (tetanus vaccine also uses this )

36
Q

formaldehyde detoxification

A
  • Formaldehyde cross links amino groups in proteins with other nearby nitrogen atoms in proteins through a CH2 linkage
  • Both intramolecular cross-linking and cross-linking between adjacent protein molecules
  • Physically changing structure of protein to prevent toxic action, but preserve its shape enough so that the immune system can mount an accurate response
37
Q

formaldehyde detoxification simple

A

-causes cross bridges to form, making a complex of toxins unable to cause harmq

38
Q

why is formaldehyde detoxification not always the best technology

A
  • too much cross linking can change structure too much
  • too little may mean it is still toxic
  • batch variation
  • reversion- cross bridges breaking releasing monomers
  • requires pure toxin at the starting point
  • need to grow and purify pathogen-dangerous
39
Q

example of multiple sub-unit vaccines

A

plague and Yesinia pestis

40
Q

example pandemics of the plague

A
  • The Justinian plague (AD542-AD570)
  • The Black Death (killed a third of European population) (14th-16th century)
  • The third pandemic- continues yto be a problem in parts of the world (Mid 19th century)
41
Q

where is Yersina pestis still rife

A

N.America, SE Asia, Madagascar

- in these parts of the world diseases are maintained in rodent reservoirs

42
Q

which are the two key protective components used in vaccines against the plague

A

F1 antigen and v antigen

43
Q

F1 antigen

A

capsule which prevents phagocytosis

44
Q

V antigen

A

Type II secretory system- a molecular syringe which are structured in bacterial cell wall and inject toxic proteins into the host cell

45
Q

hwo ar eF1 anfd V antigens produced

A

via genetic engineering

  • production mediated using antibodies
  • transferring antibodies from vaccine mice can protect against disease- proving that antibodies are protective against the plagye
46
Q

the plague vaccine is in hbuman trial

A

2 dose schedule- day 1 and 2

- competed phase 1 in humans

47
Q

F1 or V alone

A

induces protection against low challenge doses

48
Q

F1 and V together

A

induce solid protection

49
Q

how do we find the protective protein sub-unit

A
  • Decades of research on understating how the pathogen causes disease
  • Trial and error
50
Q

a modern approach to subunit vaccines

A
  • modify the toxin using genetic engineering so that is non-toxic
  • genetic toxoids
51
Q

what is a genetic toxoid

A

a genetically modified non-toxic toxin

52
Q

example of a genetic toxoid

A

diphtheria toxin CRM197

  • mutation in catalytic A subunit blocks activity
  • glycine to glutamine acid substitution at residue 52
53
Q

benefits of genetic toxoids

A
  • no issues of reversion
  • can be reproduced in a harmless E.coli
  • high yields- ease of purification
  • molecular structure more similar to active toxin

-reproducible properties

  • no batch to batch variation, product always works in the same way- reproducible
  • very effective
54
Q

reverse vaccinology in bacterial virsuses

A
  • You take a genome sequence of a microorganism and try and predict which of the proteins would be effective for inclusion in a vaccine
    o Important proteins will be found on surface of the bacteria- for an immune response
    o Predict which of the proteins encoded on the genome will end up on the outside of the cell
  • Use pSORT

o Looks at every open-reading frame and predicts the structure of the protein and looks to see if it has the right features (single features, altered amino acid composition etc), which means its likely to be on the surface.
o Can build a list of proteins likely to be on the surface

55
Q

Neisseria meningitides B causes how many death globally

A

1.2 mill invasive disease and causes and 135,000 deaths per year

56
Q

which approach to produce a vaccine for N.meningitides B

A

reverse vaccinology

57
Q

what vaccine produced for N.meningitides

A

4CMenB - via reverse vaccinology

58
Q

which strain of neisseria meningitides B cause disease in europe, nz, australia, argentina, canada and japan

A

serogoup B

59
Q

traditional vaccinology has failed to

A

identify a vaccine for Neisseria meningitides B

60
Q

describe MenB reverse vaccinology

A

1) MenB genome sequenced (3500 ORFs)
2) 570 ORFs identified encoding putative secreted/ exported proteins
3) express and purify 350 protein
4) Immunise mice and harvet sera
5) confirm surface location
6) test for bactericidal activity
7) 28 candidates for further testing

61
Q

reverse vaccinology predicts vaccine from

A

the genome sequence

62
Q

why does reverse vaccinology focus on surface antigens

A

due to being what the innate and adaptive immune system use to identify pathogens

63
Q

what can be used to predict cellular location of proteins found in ORFs

A

pSORt

64
Q

4CMenB is a vaccine for

A

meningococcal strains that cause meningitis B

65
Q

which proteins are found within a 4CMenB vaccine

A

H binding protein (fHbp), fused with NA2091 protein, binds human factor H, a negative regulator of the alternative pathway of complement activation.

NadA, major adhesion protein involved in colonization, invasion, and induction of pro-inflammatory cytokines.

NHBA, heparin-binding protein that increases resistance against the bactericidal activity of human serum

PorA 1.4 Porin, A major outer membrane protein and the target for bactericidal antibodies

66
Q

H binding protein (fHbp), fused with NA2091 protein, binds human factor H,

A

binds human factor H, a negative regulator of the alternative pathway of complement activation.

67
Q

NadA

A

major adhesion protein involved in colonization, invasion, and induction of pro-inflammatory cytokines.

68
Q

NHBA

A

eparin-binding protein that increases resistance against the bactericidal activity of human serum

69
Q

PorA 1.4 Porin

A

A major outer membrane protein and the target for bactericidal antibodies

CBI - UOE (61 decks)

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