Brief interview with Professor Mark Hatherill regarding TB vaccines

Recent Mycobacterium tuberculosis (TB) infection confers a predisposition to the development of tuberculosis disease, the #1 killer among global infectious diseases. A recent New England Journal of Medicine trial funded by Aeras and others aimed to address this deadly airborne killer.

Vaccines that prevent TB infection in young adults could have a major effect on the control of TB by interrupting transmission, but the development of new vaccines has been hampered by the lack of preclinical models and human immune correlates of protection.  Vaccine-mediated prevention of M. tuberculosis infection could be an important efficacy signal against tuberculosis disease.

A QuantiFERON-TB Gold In-tube assay (QFT) was performed to determine if trial participants acquired M. tuberculosis infection, as defined by initial conversion on the QFT test. H4:IC31, a candidate subunit vaccine, has shown protection against tuberculosis disease in preclinical models, and observational studies have indicated that primary bacille Calmette–Guérin (BCG) vaccination may offer partial protection against infection.

In this trial, the rate of sustained QFT conversion, which may reflect sustained M. tuberculosis infection, was reduced by vaccination in a high-transmission setting.

I asked Professor Mark Hatherill, Director of South African Tuberculosis Vaccine Initiative (SATVI) — University of Cape Town, a few questions. His responses are below.

  1. The study has shown us that it is possible to prevent sustained Mtb infection in humans by means of vaccination, which offers an opportunity to test other candidate TB vaccines using a prevention-of-infection clinical trial design; in the case of the H4:IC31 candidate, although the efficacy signal was modest, this is the first time that we have observed any biological evidence of efficacy of a protein subunit TB vaccine in humans, which is encouraging for development of similar vaccine candidates; and in the case of BCG, the convincing efficacy signal against sustained Mtb infection warrants re-evaluation of BCG revaccination of uninfected persons as a strategy to prevent TB disease.
  2. Next steps include modelling of the potential epidemiological impact of BCG revaccination of uninfected populations across different ages, geography, and TB burden settings; and ultimately to seek funding for a follow-up trial/s to test the efficacy of BCG revaccination (and potentially other candidate vaccines) against TB disease in this population.
  3. Funding commitment – see above. TB is global infectious disease killer #1, yet TB vaccine development has historically suffered from chronic underfunding. The next stage of TB vaccine clinical trials will need a major boost in funding to answer these important efficacy questions.

What do you think? Please share on social media or with colleagues/friends if you found this post useful.

Regards, Phil

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