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MICR334 module 3 > features of a good vaccine > Flashcards

features of a good vaccine Flashcards

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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
how does MPL act as an adjuvnat?
monophosphoryl lipid A- TLR4 agonist
26
how does CpG act as an adjuvant?
Synthetic (or already in DNA vaccine)- TLR9 agonist
27
how does MF59 act as an adjuvant?
oil in water emulsion - DC activation
28
how does Imiquimod act as an adjuvant?
TLR7 agonist
29
how can toxins act as adjuvants?
Pertussis toxin- downregulates Treg activity
30
what adjuvants are FDA approved?
Alum MPL Pertussis toxin
31
what happens in bronchiolotis?
In bronchiolitis, the airway becomes obstructed from swelling of the bronchiole walls
32
what are the features of respiratory Syncytial virus?
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
what happened in the 1960s RSV vaccine disaster?
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
what happens without string TLR stimulation (from an adjuvant)?
low antibody avidity antibody is produced
35
how was the FI RSV vaccine inducing an inappropriate immunity?
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
what organism is HIV?
Virus
37
what is the infection route of HIV?
Mucosal/Blood
38
what is the life cycle of HIV?
Mostly intracellular, integrates with host DNA
39
what is the immune protection correlations of HIV?
Very few examples of natural immunity. Neutralising antibody = difficult to generate, CD8 T cells
40
what organism is TB?
Bacterium
41
what is the infection route of TB?
Mucosal
42
what is the life cycle of TB?
Mostly intracellular, latent forms
43
what is the immune protection correlations of TB?
Very few examples of natural immunity. IFN-gamma production by T cells = unsatisfactory
44
what organism is malaria?
Eukaryotic parasite
45
what is the infection route of malaria?
Blood
46
what is the life cycle of malaria?
Complex life cycle. Intracellular and extracellular stages
47
what is the immune protection correlations of malaria?
Natural immunity is short lived
48
what are the animal models that can be used for HIV?
SIV or SHIV- macaques
49
what is the vaccine developed of HIV?
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
what are the disease models of TB?
Mouse Rabbit Guinea-pig Cattle Deer Non-human primates
51
what is the vaccine development of TB?
MVA85A Vaccine Trial failure 2013 M72 + AS01E Phase IIb (subunit vaccine + liposome adjuvant)
52
what are the disease models of malaria?
Rodent models Non-human primates
53
what is the history of vaccine development for malaria?
Last year a vaccine (R21) showed 77% efficacy in a small trial in children- VLP targets the sporozoite stage
54
what is the structure of SARS-CoV-2?
Nucleic acid surrounded by protein and a viral envelope ~120nm
55
how does SARS-CoV-2 infect a host cell?
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
how do antibodies stop SARS-CoV-2 from infecting cells?
Anti-spike antibody - prevent the spike from binding to the Ace2 receptor
57
how do RNA vaccines prevent COVID-19?
the RNA enters the body in liponanoparticles The RNA is translated to produce spike proteins that activates B cells
58
what is BNT162b2?
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
what is the role of prefusion antibody?
Lock spike primer into pre-fusion conformation so that they are recognised by the B cel before they bind
60
what is the problem with inactivated virus vaccines?
It is known that they can have inappropriate immune responses
61
what are some inactivated vaccines against?
RSV SARS MERS feline coronaviruses
62
what is immune-complex-base disease enhancement?
inactivated vaccine used in combination with an adjuvant
63
what is antibody-mediated disease enhancement?
virus is taken up by FC receptors on the host cells - would facilitate infection into a phagocytic cell
64
what is a heterologous prime-boost?
more than one vaccine used to prevent infection
65
what are the features of heterologous prime-boost?
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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