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Cited by 46Tuberculosis Research and EpidemiologyImmune responses and vaccinationsPoxvirus research and outbreaks

Effects of MVA85A vaccine on tuberculosis challenge in animals: systematic review

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Kashangura, Rufaro, Sena, Emily S, Young, Taryn, Garner, Paul·2015·International Journal of Epidemiology
DOI 10.1093/ije/dyv142PMC PMC4689998
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Abstract

BACKGROUND: The existing Bacillus Calmette–Guérin (BCG) vaccination provides partial protection against tuberculosis (TB). The modified vaccinia ankara virus-expressing antigen 85A (MVA85A) aims to boost BCG immunity. We evaluated the animal evidence supporting the testing of MVA85A in humans. METHODS: Our protocol included in vivo preclinical studies of the MVA85A booster with BCG compared with BCG alone, followed by a TB challenge. We used standard methods for systematic review of animal studies, and summarized mortality, measures of pathology and lung bacterial load. The comprehensive literature search was to September 2014. Two independent investigators assessed eligibility and performed data extraction. We assessed study quality and pooled bacteria load using random effect meta-analysis. FINDINGS: We included eight studies in 192 animals. Three experiments were in mice, two in guinea pigs, two in macaques and one in calves. Overall, study quality was low with no randomization, baseline comparability not described and blinding not reported. For animal death (including euthanasia due to severe morbidity), studies were underpowered, and overall no benefit demonstrated. No difference was shown for lung pathology measured on an ordinal scale or bacterial load. The largest mortality trial carried out in macaques had more deaths in the MVA85A vaccine group, and was published after a trial in South Africa had started recruiting children. CONCLUSIONS: This independent assessment of the animal data does not provide evidence to support efficacy of MVA85A as a BCG booster. More rigorous conduct and reporting of preclinical research are warranted, and we believe the results of studies should be publicly available before embarking on trials in humans, irrespective of the findings.

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  • In a systematic review of the effect of the MVA85A vaccine on tuberculosis challenge in animals, the largest preclinical trial did not include the vaccine name in the abstract or keywords of the publication; the paper was only included in the systematic review following discussions with experts in the field.

    “For example, in a systematic review of the effect of the MVA85A vaccine on tuberculosis challenge in animals, the largest preclinical trial did not include the vaccine name in the abstract or keywords of the publication; the paper was only included in the systematic review following discussions with experts in the field [157].”

    From Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0 (2020) · cites this paper as [157]

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Research works printed but not linked: 26

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Authors
Kashangura, R., Sena, E. S., Young, T., & Garner, P.
Affiliations
  • Stellenbosch University (ZA)
  • Florey Institute of Neuroscience and Mental Health (AU)
  • South African Medical Research Council (ZA)
  • Liverpool School of Tropical Medicine (GB)
Corresponding author
Kashangura, Rufaro
ORCID
Venue
International Journal of Epidemiology
Publisher
Oxford University Press (OUP)
Published
2015-09-08
Volume
44
Issue
6
Pages
1970-1981
ISSN
  • 0300-5771 (ISSN-L)
  • 1464-3685
DOI
10.1093/ije/dyv142
PMC
PMC4689998
OpenAlex
W2160598742
Cited by
46
References
1
Citations by year
2026: 1 · 2025: 4 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 6 · 2019: 5 · 2018: 12 · 2017: 1 · 2016: 8 · 2015: 2
FWCI
1.16
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • International Journal of Epidemiology (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LSTM Online Archive (Liverpool School of Tropical Medicine) (acceptedVersion)
Funders
  • Health Resources and Services Administration
  • U.S. Public Health Service (T84HA21652)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
  • Life Sciences › Immunology and Microbiology › Virology › Poxvirus research and outbreaks
Keywords
tuberculosis, Ag85A, lung bacterial load, vaccine efficacy, trial quality assessment, macaque, mice, guinea pig, calves
MeSH terms
Animals, Cattle, Disease Models, Animal, Guinea Pigs, Lung, Macaca, Mycobacterium tuberculosis, Tuberculosis, Tuberculosis, Pulmonary, Vaccines, DNA, Tuberculosis Vaccines, Mice, Bacterial Load

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