Flashcards in TB Vaccines Deck (36):
What is a vaccine?
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
What is the BCG vaccine?
What type of immunity does BCG induce?
cell and antibody mediated immunity
What are the benefits of the BCG?
very safe; protects against childhood TB meningitis and other disseminated disease; protection against leprosy and bladder cancer
What are the problems with BCG?
injectable; limited duration of immunity; variable efficacy; limited antigenic repetroire; interference with diagnosis; safety in immunocompromised
What is the efficacy rate against pulmonary TB with BCg?
What are the possible explanations for such variations in efficacy with BCg?
BCG strain variation; environmental mycobacteria; population genetics; nutrition; other infections
Why is there such global variation in BCG strains?
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
What is the role of environmental mycobacterial in BCG?
sensitisation with environmental mycobacteria can influence BCG replication and so protective efficacy
How does BCG interefere with TB diagnosis?
Mantoux tuberculin skin test can be false positive
Which patients particularly are there concerns with safety of BCG?
children with HIV- can cause disseminated BCG disease and protective effects in these patietns is not understood
What are the 3 vaccination strategies in TB?
pre-exposure; post-exposure and therapeutic vaccination
What does the RD1 encode?
T7SS- secretion system apparatus
What is the purpose of phase I clinical trials?
small scale to assess vaccine safety in humans and the immune reponse it stimualtes
What is the difference between phase Ia and phase Ib trials?
1a- non-endemic areas vs Ib- endemic
What is the purpose of phase II trials?
What is the first subunit vaccine in clinical trials?
What is MVA85A?/
modified vaccinia virus and a simple mycobacterial antigen put in
What were the efficacy results of MVA85A?
induced modest cell-mediated immune responses but no efficacy against M.tb infection
What is the benefit of GSK Mtb72F/AS02A?
a subunit vaccine so safe in HIV patients
What is the Mtb72F/AS02A vaccine?
fusion protein of PPE and inactive protease formulated in liposomal adjuvant AS02A
What was foudn to be the results of efficacy of Mtb72F/AS02A?
54% protection against active pulmonary TB
What is the VPM1002?
recombinant BCG lacking the urease C gene but expressing listeriolysin
What is the function of listeriolysin in VPM1002?
promotes antigen translocation to cytoplasm and enhanced apoptosis and antigen cross-ppresentation
What is the function of urease C?
blocks the decrease of pH in the endosome
What is the only live-attenuated M.tb vaccine?
What are hte 2 genetic deletions in MTBVAC?
phoP and fadD26
What si the function of phoP?
transcription that controls more than 2% of Mtb genome such as the virulence factor ESAT-6/CFP10
What is the function of fadD26?
involved in synthesis of the major cell wall lipid phthiocerol dimycocerosate (PDIM)
What happens when there is disturbance in tight immune regulation of a solid granuloma?
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
What is the specificity of yd T cells?
small pyrophosphate-containing metabolites
What is the general function of subunit TB vaccines?
boosters after BCG vaccination
Which type of T cell are not stimulated by BCG?
CD8 T cells
What are the mechanisms by which VPM1002 enhances antigen processing and presentation?
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)
What are the myeloid-derived suppressor cells characterised by?
M1 marker- iNOS and M2 marker- arginase 1 --not a distinct subset but a developmental stage of certain neutrophilic and monocytic phagocytes