MVA85A

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MVA85A (modified vaccinia Ankara 85A) is a vaccine against tuberculosis developed by researchers led by Professor Helen McShane at Oxford University. [1] It is a viral vector vaccine and consists of an MVA virus engineered to express the 85A antigen once it infects a host cell. 85A is a cell-wall protein of the tuberculosis bacillus.

This vaccine produces higher levels of long-lasting cellular immunity when used together with the older TB vaccine BCG. [2] Phase I clinical trials were completed in 2008 and then phase II clinical trials took place in South Africa. [3] [4] Efficacy trials ran in parallel from 2009 to 2019. [5] Results released in February 2013 were described as "disappointing", showing only a statistically insignificant prevention rate in infants. [6] A summary of animal studies published in 2015 cast doubt on the efficacy of the vaccine. [7]

In 2018, a BMJ investigation raised concerns about the ethics of an efficacy trial in South African infants, particularly because of results from earlier animal trials such as a study with macaques at Porton Down. [8] One response argued that 14 prior human trials showed a safety signal, that regulators were aware of the primate trial and decided to continue, and that three subsequent investigations found no evidence of wrong-doing. [9] Another response by Ian Orme questioned the critique of animal models. [10]

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References

  1. ↑ "Professor Helen McShane FMedSci FRCP". Nuffield Department of Medicine, Medical Sciences Division. Retrieved 2019-07-01.
  2. ↑ McShane H, Pathan AA, Sander CR, et al. (2004). "Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG primed and naturally acquired anti-microbial immunity in humans". Nat Med. 10 (11): 1240–44. doi: 10.1038/nm1128 . PMID   15502839.
  3. ↑ Hawkridge T, Scriba TJ, Gelderbloem S, et al. (2008). "Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in healthy adults in South Africa". J Infect Dis. 198 (4): 544–52. doi:10.1086/590185. PMC   2822902 . PMID   18582195.
  4. ↑ Ibanga H, Brookes R, Hill P, Owiafe P, Fletcher H, Lienhardt C, Hill A, Adegbola R, McShane H (2006). "Early clinical trials with a new tuberculosis vaccine, MVA85A, in tuberculosis-endemic countries: issues in study design". Lancet Infect Dis. 6 (8): 522–8. doi:10.1016/S1473-3099(06)70552-7. PMID   16870530.
  5. ↑ McShane H (23 September 2010). "Improving BCG with MVA85A: An update on clinical trials" (PDF). The Jenner Institute. Archived from the original (PDF) on 14 August 2013. Retrieved 2 October 2012.
  6. ↑ Walsh, Fergus (4 February 2013). "Tuberculosis vaccine hopes dashed". BBC News. Retrieved 4 February 2013.
  7. ↑ "Effects of MVA85A vaccine on tuberculosis challenge in animals: systematic review". Ije.oxfordjournals.org. Retrieved 2015-09-09.[ dead link ]
  8. ↑ Cohen, Deborah (2018-01-10). "Oxford TB vaccine study calls into question selective use of animal data". BMJ. 360: j5845. doi:10.1136/bmj.j5845. ISSN   0959-8138. PMID   29321165. S2CID   196494376.
  9. ↑ Ginsberg, Ann; Shea, Jacqui; Tameris, Michele; Hatherill, Mark; Hill, Adrian; McShane, Helen (2018-01-26). "Helen McShane and colleagues reply to Deborah Cohen". BMJ (Letters). 360: k236. doi:10.1136/bmj.k236. ISSN   0959-8138. PMID   29374008. S2CID   46783593.
  10. ↑ Orme, Ian M. (2019-07-01). "Re: Helen McShane and colleagues reply to Deborah Cohen". The BMJ (Letters).


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