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Module 2 > TB Vaccines > Flashcards

TB Vaccines Flashcards

1
Q

What is a vaccine?

A

preparation of killed microbes; living attenuated organsims or living fully virulent organisms or part therof that is administered to produce or artificially increase immunity to a disease

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2
Q

What is the BCG vaccine?

A

attenuated M.bovis

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3
Q

What type of immunity does BCG induce?

A

cell and antibody mediated immunity

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4
Q

What are the benefits of the BCG?

A

very safe; protects against childhood TB meningitis and other disseminated disease; protection against leprosy and bladder cancer

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5
Q

What are the problems with BCG?

A

injectable; limited duration of immunity; variable efficacy; limited antigenic repetroire; interference with diagnosis; safety in immunocompromised

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6
Q

What is the efficacy rate against pulmonary TB with BCg?

A

0-80%

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7
Q

What are the possible explanations for such variations in efficacy with BCg?

A

BCG strain variation; environmental mycobacteria; population genetics; nutrition; other infections

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8
Q

Why is there such global variation in BCG strains?

A

when first created in Pasteur institute. no seed lots (no freeze drying) so was taken back and cultured in different countries resulting in mutations and different strains

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9
Q

What is the role of environmental mycobacterial in BCG?

A

sensitisation with environmental mycobacteria can influence BCG replication and so protective efficacy

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10
Q

How does BCG interefere with TB diagnosis?

A

Mantoux tuberculin skin test can be false positive

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11
Q

Which patients particularly are there concerns with safety of BCG?

A

children with HIV- can cause disseminated BCG disease and protective effects in these patietns is not understood

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12
Q

What are the 3 vaccination strategies in TB?

A

pre-exposure; post-exposure and therapeutic vaccination

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13
Q

What does the RD1 encode?

A

T7SS- secretion system apparatus

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14
Q

What is the purpose of phase I clinical trials?

A

small scale to assess vaccine safety in humans and the immune reponse it stimualtes

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15
Q

What is the difference between phase Ia and phase Ib trials?

A

1a- non-endemic areas vs Ib- endemic

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16
Q

What is the purpose of phase II trials?

17
Q

What is the first subunit vaccine in clinical trials?

18
Q

What is MVA85A?/

A

modified vaccinia virus and a simple mycobacterial antigen put in

19
Q

What were the efficacy results of MVA85A?

A

induced modest cell-mediated immune responses but no efficacy against M.tb infection

20
Q

What is the benefit of GSK Mtb72F/AS02A?

A

a subunit vaccine so safe in HIV patients

21
Q

What is the Mtb72F/AS02A vaccine?

A

fusion protein of PPE and inactive protease formulated in liposomal adjuvant AS02A

22
Q

What was foudn to be the results of efficacy of Mtb72F/AS02A?

A

54% protection against active pulmonary TB

23
Q

What is the VPM1002?

A

recombinant BCG lacking the urease C gene but expressing listeriolysin

24
Q

What is the function of listeriolysin in VPM1002?

A

promotes antigen translocation to cytoplasm and enhanced apoptosis and antigen cross-ppresentation

25
Q

What is the function of urease C?

A

blocks the decrease of pH in the endosome

26
Q

What is the only live-attenuated M.tb vaccine?

27
Q

What are hte 2 genetic deletions in MTBVAC?

A

phoP and fadD26

28
Q

What si the function of phoP?

A

transcription that controls more than 2% of Mtb genome such as the virulence factor ESAT-6/CFP10

29
Q

What is the function of fadD26?

A

involved in synthesis of the major cell wall lipid phthiocerol dimycocerosate (PDIM)

30
Q

What happens when there is disturbance in tight immune regulation of a solid granuloma?

A

there is cell death and necrosis leading to caseation which then fails to control Mtb which can grwo in the necrotic detritus in the centre of hte lesion

31
Q

What is the specificity of yd T cells?

A

small pyrophosphate-containing metabolites

32
Q

What is the general function of subunit TB vaccines?

A

boosters after BCG vaccination

33
Q

Which type of T cell are not stimulated by BCG?

A

CD8 T cells

34
Q

What are the mechanisms by which VPM1002 enhances antigen processing and presentation?

A

apoptosis and xenophagy are known to improve this; apoptosis- pertubated endosomal membrane by listeriolysin allows realase of lysosomal enzymes causing apoptosis; xenophagy is stimulated by release of dsDNA into cytosol which stimulate AIM2 and STING causes LC3-II expression (indicator of xenophagy)

35
Q

What are the myeloid-derived suppressor cells characterised by?

A

M1 marker- iNOS and M2 marker- arginase 1 –not a distinct subset but a developmental stage of certain neutrophilic and monocytic phagocytes

36
Q

What is the role of MDSCs in tB?

A

seen in higher numbers in susceptbile mice- inhibit secretion of protective IFNy by T cells

Module 2 (38 decks)

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