TB Vaccines

Question 1

What is a vaccine?

Answer 1

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

Question 2

What is the BCG vaccine?

Answer 2

attenuated M.bovis

Question 3

What type of immunity does BCG induce?

Answer 3

cell and antibody mediated immunity

Question 4

What are the benefits of the BCG?

Answer 4

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

Question 5

What are the problems with BCG?

Answer 5

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

Question 6

What is the efficacy rate against pulmonary TB with BCg?

Answer 6

0-80%

Question 7

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

Answer 7

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

Question 8

Why is there such global variation in BCG strains?

Answer 8

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

Question 9

What is the role of environmental mycobacterial in BCG?

Answer 9

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

Question 10

How does BCG interefere with TB diagnosis?

Answer 10

Mantoux tuberculin skin test can be false positive

Question 11

Which patients particularly are there concerns with safety of BCG?

Answer 11

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

Question 12

What are the 3 vaccination strategies in TB?

Answer 12

pre-exposure; post-exposure and therapeutic vaccination

Question 13

What does the RD1 encode?

Answer 13

T7SS- secretion system apparatus

Question 14

What is the purpose of phase I clinical trials?

Answer 14

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

Question 15

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

Answer 15

1a- non-endemic areas vs Ib- endemic

Question 16

What is the purpose of phase II trials?

Answer 16

efficacy

Question 17

What is the first subunit vaccine in clinical trials?

Answer 17

MVA85A

Question 18

What is MVA85A?/

Answer 18

modified vaccinia virus and a simple mycobacterial antigen put in

Question 19

What were the efficacy results of MVA85A?

Answer 19

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

Question 20

What is the benefit of GSK Mtb72F/AS02A?

Answer 20

a subunit vaccine so safe in HIV patients

Question 21

What is the Mtb72F/AS02A vaccine?

Answer 21

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

Question 22

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

Answer 22

54% protection against active pulmonary TB

Question 23

What is the VPM1002?

Answer 23

recombinant BCG lacking the urease C gene but expressing listeriolysin

Question 24

What is the function of listeriolysin in VPM1002?

Answer 24

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

Question 25

What is the function of urease C?

Answer 25

blocks the decrease of pH in the endosome

Question 26

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

Answer 26

MTBVAC

Question 27

What are hte 2 genetic deletions in MTBVAC?

Answer 27

phoP and fadD26

Question 28

What si the function of phoP?

Answer 28

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

Question 29

What is the function of fadD26?

Answer 29

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

Question 30

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

Answer 30

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

Question 31

What is the specificity of yd T cells?

Answer 31

small pyrophosphate-containing metabolites

Question 32

What is the general function of subunit TB vaccines?

Answer 32

boosters after BCG vaccination

Question 33

Which type of T cell are not stimulated by BCG?

Answer 33

CD8 T cells

Question 34

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

Answer 34

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)

Question 35

What are the myeloid-derived suppressor cells characterised by?

Answer 35

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

Question 36

What is the role of MDSCs in tB?

Answer 36

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