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

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Kashangura, Rufaro, Sena, Emily, Young, Taryn and Garner, Paul ORCID: https://orcid.org/0000-0002-0607-6941 (2015) 'Effects of MVA85A vaccine on tuberculosis challenge in animals: systematic review'. International Journal of Epidemiology, Vol 44, Issue 6, pp. 1970-1981.

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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.

Item Type: Article
Subjects: QW Microbiology and Immunology > Reference Works. General Immunology > QW 520 Research (General)
QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 805 Vaccines. Antitoxins. Toxoids
QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 806 Vaccination
WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General)
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1093/ije/dyv142
Depositing User: Christianne Esparza
Date Deposited: 16 Sep 2015 13:26
Last Modified: 06 Sep 2019 10:15
URI: https://archive.lstmed.ac.uk/id/eprint/5312

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