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MICR334 module 3 > features of a good vaccine > Flashcards

features of a good vaccine Flashcards

1
Q

what are the features of cowpox?

A
  • Zoonosis
  • In humans- pustular lesions on skin; rarely fever and myalgia
  • lesions regress spontaneously
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2
Q

what is the case fatality rate of smallpox?

A

20-60%

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3
Q

what are the different types of vaccines?

A

Protein (subunit) + adjuvant
DNA or RNA vaccines
Virus vectors (adenovirus, modified vaccinia)
Virus-like particles (VLP)
Inactivated pathogens (killed, or live but weakened)

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4
Q

what is the role of a vaccine?

A

Induces memory without causing disease

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5
Q

what are the different routes of vaccination?

A

Oral or by injection: intradermal or intramuscular

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6
Q

what are the features of effective vaccines?

A
  • safe
  • protective
  • gives sustained protection
  • Induces neutralizing antibody
  • Induces protective T cells
  • Practical considerations
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7
Q

what makes a vaccine safe?

A

Vaccine must not itself cause illness or death

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8
Q

what makes a vaccine protective?

A

Vaccine must protect against illness resulting from exposure to live pathogen

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9
Q

what is vaccine-sustained protection?

A

-Protection against illness must last for several years

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10
Q

why does a vaccine need to induce neutralizing antibody?

A

Some pathogens (such as poliovirus) infect cells that cannot be replaced (e.g. neurons).
Neutralizing antibody is essential to prevent infection of such cells

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11
Q

why does a vaccine need to induce protective T cells?

A

Some pathogens, particularly intracellular, are more effectively dealt with by cell-mediated responses

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12
Q

what are the practical considerations for a vaccine?

A

Low cost per dose
Biologically stability
Ease of administration
Few side-effects

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13
Q

what needs to be considered when designing a new vaccine?

A

-the desired immune response
- route of vaccination
- mode of delivery
- Type of vaccine (desired antigen and antigen form)
- Type of adjuvant

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14
Q

how can we potentially improve vaccine delivery?

A
  • Needle-free delivery (e.g. oral vaccination)
  • Dermal delivery (microneedles)
  • Potentially safer, cheaper, more effective, more palatable to public than intramuscular delivery
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15
Q

what are the dermal types of vaccine delivery?

A
  • Transcutaneous (patch +/- pretreatment with microneedles or abrasion
  • Epidermal (microneedles, jet injectors)
  • Intradermal (fine syringes, microinjection)
  • Percutaneous (multiple-puncture with short needles)
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16
Q

what structures are involved in mucosal delivery?

A
  • Virus-like particles
  • Liposomes
  • Synthetic polymers
  • Lipids
  • Attenuated organsim
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17
Q

what is the visual system?

A

cornea

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18
Q

what is the alimentary system?

A

mouth
esophagus

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19
Q

what is the respiratory system?

A

nasal cavity, lung
Small intestine, large intestine

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20
Q

what is involved in the upper female reproductive system?

A

Endocervix, uterus, oviduct, ovary

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21
Q

what is the lower female reproductive system?

A

ectocervix, vagina

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22
Q

what are some adjuvants?

A

TLR/NLR agonists
Toxins

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23
Q

what are some examples of TLR/NLR agonists?

A

Alum
MPL
CpG
MF59
Imiquimod

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24
Q

how does alum act as an adjuvant?

A

aluminium salts- triggers NALP3 inflammasome

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25
Q

how does MPL act as an adjuvnat?

A

monophosphoryl lipid A- TLR4 agonist

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26
Q

how does CpG act as an adjuvant?

A

Synthetic (or already in DNA vaccine)- TLR9 agonist

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27
Q

how does MF59 act as an adjuvant?

A

oil in water emulsion - DC activation

28
Q

how does Imiquimod act as an adjuvant?

A

TLR7 agonist

29
Q

how can toxins act as adjuvants?

A

Pertussis toxin- downregulates Treg activity

30
Q

what adjuvants are FDA approved?

A

Alum
MPL
Pertussis toxin

31
Q

what happens in bronchiolotis?

A

In bronchiolitis, the airway becomes obstructed from swelling of the bronchiole walls

32
Q

what are the features of respiratory Syncytial virus?

A

Pneumovirus of paramyxoviridae family
- causes bronchiolitis in winter epidemics (>90% of infants infected before age 2)
- 1/1000 infected infants die

sRNA, -ve sense genome of ten genes, 15,000 nucleotides

33
Q

what happened in the 1960s RSV vaccine disaster?

A

Despite the formalin-inactivated RSV vaccine inducing high antibody titres, 18/31 vaccinees required hospilisation when naturally exposed to the virus, 2 of these infants dies

Post mortem fincings: extensive bronchopneumonia , monocytic and eosinophilic infiltrate

34
Q

what happens without string TLR stimulation (from an adjuvant)?

A

low antibody avidity antibody is produced

35
Q

how was the FI RSV vaccine inducing an inappropriate immunity?

A

FI RSV induced a low avidity RSV-specific antibody response, a strong RSV-specific CD4+ T cell response and no cytotoxic CD8+ T cell response

The antibody complexes activated complement components which, together with the CD4+ T cell response, drove the unsuccessful inflammatory response

36
Q

what organism is HIV?

A

Virus

37
Q

what is the infection route of HIV?

A

Mucosal/Blood

38
Q

what is the life cycle of HIV?

A

Mostly intracellular, integrates with host DNA

39
Q

what is the immune protection correlations of HIV?

A

Very few examples of natural immunity. Neutralising antibody = difficult to generate, CD8 T cells

40
Q

what organism is TB?

A

Bacterium

41
Q

what is the infection route of TB?

A

Mucosal

42
Q

what is the life cycle of TB?

A

Mostly intracellular, latent forms

43
Q

what is the immune protection correlations of TB?

A

Very few examples of natural immunity. IFN-gamma production by T cells = unsatisfactory

44
Q

what organism is malaria?

A

Eukaryotic parasite

45
Q

what is the infection route of malaria?

A

Blood

46
Q

what is the life cycle of malaria?

A

Complex life cycle. Intracellular and extracellular stages

47
Q

what is the immune protection correlations of malaria?

A

Natural immunity is short lived

48
Q

what are the animal models that can be used for HIV?

A

SIV or SHIV- macaques

49
Q

what is the vaccine developed of HIV?

A

STEP Vaccine Trial (Adenovirus 5) failure 2007

HVTN 505 (DNA prime, Ad5 boost) failure 2013

RV144 (Canary pos prime - rec protein boost) - some success

50
Q

what are the disease models of TB?

A

Mouse
Rabbit
Guinea-pig
Cattle
Deer
Non-human primates

51
Q

what is the vaccine development of TB?

A

MVA85A Vaccine Trial failure 2013

M72 + AS01E Phase IIb (subunit vaccine + liposome adjuvant)

52
Q

what are the disease models of malaria?

A

Rodent models
Non-human primates

53
Q

what is the history of vaccine development for malaria?

A

Last year a vaccine (R21) showed 77% efficacy in a small trial in children- VLP targets the sporozoite stage

54
Q

what is the structure of SARS-CoV-2?

A

Nucleic acid surrounded by protein and a viral envelope
~120nm

55
Q

how does SARS-CoV-2 infect a host cell?

A

SARS-CoV-2 must bind to a human cell surface protein- the ACE2 receptor- by using its spike protein

The virus then enters the cell and hijacks the cell’s machinery to reproduce and produce thousands of new infections virsues

The human host is infected

56
Q

how do antibodies stop SARS-CoV-2 from infecting cells?

A

Anti-spike antibody
- prevent the spike from binding to the Ace2 receptor

57
Q

how do RNA vaccines prevent COVID-19?

A

the RNA enters the body in liponanoparticles
The RNA is translated to produce spike proteins that activates B cells

58
Q

what is BNT162b2?

A

A lipid nanopartible containing mRNA that encodes the full length spike protein from SARS-CoV-2

  • it includes 2 proline mutations that lock the spike trimer into a “prefusion” conformation

-Upon binding to ACE2 the normal spike trimer is cleaved and folds irreversibly into a post-fusion conformation- this can also happen spontaneously

59
Q

what is the role of prefusion antibody?

A

Lock spike primer into pre-fusion conformation so that they are recognised by the B cel before they bind

60
Q

what is the problem with inactivated virus vaccines?

A

It is known that they can have inappropriate immune responses

61
Q

what are some inactivated vaccines against?

A

RSV
SARS
MERS
feline coronaviruses

62
Q

what is immune-complex-base disease enhancement?

A

inactivated vaccine used in combination with an adjuvant

63
Q

what is antibody-mediated disease enhancement?

A

virus is taken up by FC receptors on the host cells
- would facilitate infection into a phagocytic cell

64
Q

what is a heterologous prime-boost?

A

more than one vaccine used to prevent infection

65
Q

what are the features of heterologous prime-boost?

A

Can be more effective than homologous prime-bopst

Can use different routes of administration for prime and boost
- Spike-trimer (protein) + cGAMP (adjuvant- STING agonist) IN
- Ad5 encoding Spike IN
- mRNA-LNP IM

MICR334 module 3 (6 decks)

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