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
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.
This research is supported by the Department for International Development’s Evidence Building and Synthesis Research Programme which is led by Liverpool School of Tropical Medicine
Kashangura, R.; Sena, E.S.; Young, T.; Garner, P. Effects of MVA85A vaccine on tuberculosis challenge in animals: systematic review. International Journal of Epidemiology (2015) 44 (6) 1970-1981. [DOI: 10.1093/ije/dyv142]