Objectives. To investigate the safety and immunogenicity of boosting BCG
with modified vaccinia Ankara expressing antigen 85A (MVA85A), shortly
after BCG vaccination, and to compare this first with the immunogenicity
of BCG vaccination alone and second with a previous clinical trial where
MVA85A was administered more than 10 years after BCG vaccination.
Design. There are two clinical trials reported here: a Phase I
observational trial with MVA85A; and a Phase IV observational trial with
BCG. These clinical trials were all conducted in the UK in healthy, HIV
negative, BCG naıve adults. Subjects were vaccinated with BCG alone; or
BCG and then subsequently boosted with MVA85A four weeks later (short
interval). The outcome measures, safety and immunogenicity, were
monitored for six months. The immunogenicity results from this short
interval BCG prime - MVA85A boost trial were compared first with the BCG
alone trial and second with a previous clinical trial where MVA85A
vaccination was administered many years after vaccination with BCG.
Results. MVA85A was safe and highly immunogenic when administered to
subjects who had recently received BCG vaccination. When the short
interval trial data presented here were compared with the previous long
interval trial data, there were no significant differences in the
magnitude of immune responses generated when MVA85A was administered
shortly after, or many years after BCG vaccination.
Conclusions. The clinical trial data presented here provides further
evidence of the ability of MVA85A to boost BCG primed immune responses.
This boosting potential is not influenced by the time interval between
prior BCG vaccination and boosting with MVA85A. These findings have
important implications for the design of efficacy trials with MVA85A.
Boosting BCG induced anti-mycobacterial immunity in either infancy or
adolescence are both potential applications for this vaccine, given the
immunological data presented here. Trial Registration.
ClinicalTrials.gov NCT00427453 (short boosting interval), NCT00427830
(long boosting interval), NCT00480714 (BCG alone)
Pathan, A.A.; Sander, C.R.; Fletcher, H.A.; Poulton, I.; Alder, N.C.; Beveridge, N.E.R.; Whelan, K.T.; Hill, A.V.S.; McShane, H. Boosting BCG with Recombinant Modified Vaccinia Ankara Expressing Antigen 85A: Different Boosting Intervals and Implications for Efficacy Trials. PLoS ONE (2007) 2 (10) e1052. [DOI: 10.1371/journal.pone.0001052]
Boosting BCG with Recombinant Modified Vaccinia Ankara Expressing Antigen 85A: Different Boosting Intervals and Implications for Efficacy Trials.