Abstract
Background. A new vaccine is urgently needed to combat tuberculosis. However, without a correlate of protection, selection of the vaccines to take forward into large-scale efficacy trials is difficult. Use of bacille Calmette-Guérin (BCG) as a surrogate for human Mycobacterium tuberculosis challenge is a novel model that could aid selection.Methods. Healthy adults were assigned to groups A and B (BCG-naive) or groups C and D (BCG-vaccinated). Groups B and D received candidate tuberculosis vaccine MVA85A. Participants were challenged with intradermal BCG 4 weeks after those who received MVA85A. Skin biopsies of the challenge site were taken 2 weeks post challenge and BCG load quantified by culture and quantitative polymerase chain reaction (qPCR).Results. Volunteers with a history of BCG showed some degree of protective immunity to challenge, having lower BCG loads compared with volunteers without prior BCG, regardless of MVA85A status. There was a significant inverse correlation between antimycobacterial immunity at peak response after MVA85A and BCG load detected by qPCR.Conclusion. Our results support previous findings that this BCG challenge model is able to detect differences in antimycobacterial immunity induced by vaccination and could aid in the selection of candidate tuberculosis vaccines for field efficacy testing.Clinical Trials Registration NCT01194180.
Highlights
A new vaccine is urgently needed to combat tuberculosis
Volunteers with a history of bacille Calmette-Guérin (BCG) showed some degree of protective immunity to challenge, having lower BCG loads compared with volunteers without prior BCG, regardless of MVA85A status
There was a significant inverse correlation between antimycobacterial immunity at peak response after MVA85A and BCG load detected by quantitative polymerase chain reaction (qPCR)
Summary
Healthy adults were assigned to groups A and B (BCG-naive) or groups C and D (BCG-vaccinated). Groups B and D received candidate tuberculosis vaccine MVA85A. Participants were challenged with intradermal BCG 4 weeks after those who received MVA85A. Twenty-six BCG-vaccinated and 23 BCG-naive healthy volunteers aged 18–55 years were enrolled between March 2011 and November 2011 at the Centre for Clinical Vaccinology & Tropical Medicine, Churchill Hospital, Oxford, United Kingdom (see Figure 1). All participants gave written informed consent, and the trial was conducted according to the principles of the Declaration of Helsinki and Good Clinical Practice. Those enrolled were in good health, had normal baseline hematology and biochemistry, and were serologically negative for hepatitis B, hepatitis C, and HIV. One individual in group B had to withdraw from follow-up for personal reasons after
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