Rationale: An effective new tuberculosis (TB) vaccine regimen must be
safe in individuals with latent TB infection (LTBI) and is a priority
for global health care.
Objectives: To evaluate the safety and immunogenicity of a leading new
TB vaccine, recombinant Modified Vaccinia Ankara expressing Antigen 85A
(MVA85A) in individuals with LTBI.
Methods: An open-label, phase I trial ofMVA85Awas performed in 12
subjects with LTBI recruited from TB contact clinics in Oxford and
London or by poster advertisements in Oxford hospitals. Patients were
assessed clinically and had blood samples drawn for immunological
analysis over a 52-week period after vaccination with MVA85A. Thoracic
computed tomography scans were performed at baseline and at 10 weeks
after vaccination. Safety of MVA85A was assessed by clinical,
radiological, and inflammatory markers. The immunogenicity of MVA85A was
assessed by IFNg and IL-2 ELISpot assays and FACS.
Measurements and Main Results: MVA85A was safe in subjects with LTBI,
with comparable adverse events to previous trials of MVA85A. There were
no clinically significant changes in inflammatory markers or thoracic
computed tomography scans after vaccination. MVA85A induced a strong
antigen-specific IFN-g and IL-2 response that was durable for 52 weeks.
The magnitude of IFN-g response was comparable to previous trials of
MVA85A in bacillus Calmette- Gue´rin–vaccinated individuals. Antigen
85A–specific polyfunctional CD41 T cells were detectable prior to
vaccination with statistically significant increases in cell numbers
Conclusions: MVA85A is safe and highly immunogenic in individuals with
LTBI. These results will facilitate further trials in TB-endemic areas.
Sander, C.R.; Pathan, A.A.; Beveridge, N.E.R.; Poulton, I.; Minassian, A.; Alder, N.; Van Wijgerden, J.; Hill, A.V.S.; Gleeson, F.V.; Davies, R.J.O.; Pasvol, G.; McShane, H. Safety and Immunogenicity of a New Tuberculosis Vaccine, MVA85A, in Mycobacterium tuberculosis&#8211;infected Individuals. American Journal of Respiratory and Critical Care Medicine (2009) 179 (8) 724-733. [DOI: 10.1164/rccm.200809-1486OC]
Safety and Immunogenicity of a New Tuberculosis Vaccine, MVA85A, in Mycobacterium Tuberculosis–infected Individuals.