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Infection And Immunity > Unit 8: Vaccinology > Flashcards

Unit 8: Vaccinology Flashcards

1
Q

what is the hallmark of a successful vaccine?

A

a vaccine that induces an immune response which is disease preventing, long-lasting, ideally sterilising
provides a broad protection against all serotypes of a pathogen

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2
Q

what should a vaccine be?

A
  • safe
  • affordable
  • easy to administer
  • long shelf life + temp tolerant
  • DIVA compliant
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3
Q

what is DIVA?

A

differentiating infected from vaccinated animals

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4
Q

what are some of the types of vaccine?

A
  • whole organism vaccines (killed/inactivated vs live attenuated)
  • toxoid
  • subunit
  • viral vector
  • nucleic acid
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5
Q

give some examples of killed/inactivated whole organism vaccines

A
  • rabies
  • hepatitis A
  • (inactivated) polio
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6
Q

what are the pros and cons of killed/inactivated whole organism vaccines?

A
  • can’t replicate
  • simple + stable
  • shorter length immuno-protection
  • need for boosters
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7
Q

give some examples of live attenuated whole organism vaccines

A
  • MMR
  • intranasal influenza
  • BCG
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8
Q

what are the pros and cons of live attenuated whole organism vaccines?

A
  • strong + long lasting immune response
  • simple
  • disease reversion possible
  • temperature sensitive
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9
Q

give some examples of toxoid vaccines

A
  • diptheria
  • tetanus
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10
Q

what are the pros and cons of toxoid vaccines?

A
  • memory developed after first injection
  • strong immune response
  • only effective if disease caused solely by bacterial endotoxins
  • requires cold chain
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11
Q

give some examples of subunit vaccines

A
  • HPV
  • hepatitis B
  • meningococcal bacteria
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12
Q

what are the pros and cons of subunit vaccines?

A
  • no live components
  • relatively stable
  • complex and time consuming
  • low immunogenicity needing adjuvants + boosters
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13
Q

give some examples of viral vector vaccines

A
  • ebola
  • SARS-CoV2
  • canine distemper
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14
Q

what are the pros and cons of viral vector vaccines?

A
  • strong immune response (T/B response)
  • no disease risk
  • previous exposure could reduce effectiveness
  • complex
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15
Q

what is different about nucleic acid vaccines?

A
  • DNA delivered to nucleus of target cells (electroporation)
  • mRNA needs protection from degradation + use of lipid membrane
  • mRNA translation lasts few days then naturally broken down
  • mRNA moderna/pfizer vaccine
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16
Q

what are the pros and cons of nucleic acid vaccines?

A
  • no infection risk
  • simple, cost effective + heat stable
  • only protein antigens can be expressed
  • potential atypical protein processing
  • potential integration of foreign DNA into genome
17
Q

what T cell response do vaccinations induce?

A

CD4+ T cell = Th2 response

18
Q

what are some factors to consider when deciding vaccine delivery methods?

A
  • size, shape, charge, hydrophobia, receptor interacting surfaces of antigens
  • vaccine type
  • use of + type of adjuvant
  • presence of repetitive structures?
19
Q

what are some host factors that could lead to vaccine failure?

A
  • age influence
  • immunodeficiencies
  • waning immunity
  • immunological interference
20
Q

what are some vaccine factors that could lead to vaccine failure?

A
  • lack of immune response required for protection
  • incomplete coverage of strains
  • vaccine escape mutants
  • antigenic interference
  • manufacture/ storage issues
21
Q

what is a LNP?

A

lipid-based nanoparticles - used for self-assembly in mRNA vaccines

22
Q

how is the efficacy of viruses defined?

A

the measure of how much a vaccine has lowered a risk of getting sick with that pathogen

23
Q

what are some pros and cons of mRNA vaccines?

A
  • easy, rapid, safe with high efficacy
  • CD4+ + CD8+ immune response + antibodies
  • short half life
  • high cost, complex delivery and cold chain dependent
  • strong immunogenicity (ssRNA)
24
Q

what are the top 5 most deadliest human diseases?

A
  • tuberculosis (10mil, 1.5mil deaths)
  • measles (140,000 deaths)
  • malaria (228mil, >405,000 deaths)
  • influenza (3-5mil, 650,000 deaths)
  • diarrhoeal diseases (525,000 deaths)
    covid at 6 with >6.8mil deaths over 3 years
25
Q

why is it difficult to vaccinate against parasites eg plasmodium?

A
  • different protein expression at different points of the life cycle
  • large/ complex genome with immune evasion mechanisms
  • intracellular niches
  • antigen polymorphisms
  • redundant host cell invasion pathways
  • immune suppression
26
Q

what can you vaccines target at different stages of plasmodium infection?

A
  • gamete targeting within mosquito= block transmission
  • blood stage = no MHC = antibodies, CD4+ T cells, macrophages and complement
  • pre-erythrocytic = MHCI = antibodies, CD4+, CD8+, macrophages
27
Q

what does the RTS,S/AS01E vaccine for malaria target?

A

CSP (circumsporozoite protein)
basically is the hepB vaccine - recombinant CSP fused to HepBV surface antigen
is a yeast vaccine

28
Q

what was the problem with the RTS,S/AS01E vaccine? how was it improved?

A

very poor efficiacy - 36%
BUT did prevent 1774 malaria episodes per 1000 children
efficacy drops after 6 months
additional use of matrix M in vaccine = 77% efficacy + yeast changed

29
Q

why? can gametocyte + gamete surface proteins be targeted as a vaccine option?

A

antibody response will inhibit fertilization = no disease transmission

30
Q

what cells of the immune system help prevent constant inflamed gut?

A
  • M-cells = above Peyer’s patches, stimulate IgA/G
  • yS T cells
  • regulatory T cells
31
Q

why use yeast as a vesicle for oral vaccines?

A
  • cheap
  • safe
  • common in diet and available in many forms
32
Q

how does Dectin-1 and TLR2 initiate the immune system to yeast antigens?

A

Dectin-1 = uptake of antigen + production of ROS, expressed on M-cells
TLR2 = production of inflammatory mediators as antigen response

33
Q

what is the molecular basis for attenuation in the BCG vaccine?

A

RD1 (region of deletion) during attenuation = loss of ESAT-6 secretion system 1 (ESX-1) = no secretion of major protein antigens

34
Q

what are some strategies for assessing vaccine efficacy?

A
  • lab based = measure immune respose = IFNy-ELISA
  • measure protection against in vivo models via pathology scores/ bacterial load
  • population = randomised controlled + observational studies
35
Q

why does the BCG vaccine need to be improved?

A
  • limited efficacy against pulmonary TB in adults
  • only 50% protective efficacy in children
  • doesn’t protect against disease in people already infected etc
36
Q

how can antigen presentation be improved in BCG vaccine?

A
  • express listeriolysin O = phagosomal membrane perforation = in cytosol = more anitgen presentation
  • deletion of urease C = no ammonia produced = acidic environment = improved listeriolysin O

Infection And Immunity (8 decks)

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