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Safety and Immunogenicity of a New Tuberculosis Vaccine, MVA85A, in Mycobacterium tuberculosis–infected Individuals

¹ Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, and ² Centre for Statistics in Medicine, Wolfson College Annexe, University of Oxford, Oxford; ³ Ealing Primary Care Trust, Ealing; ⁴ Oxford Centre for Respiratory Medicine and Radiology, Oxford Radcliffe NHS Trust, Oxford; and ⁵ Imperial College London, Northwick Park Hospital, London, United Kingdom

Correspondence and requests for reprints should be addressed to Helen McShane, Ph.D., F.R.C.P., Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, University of Oxford, Oxford OX3 7LJ, UK. E-mail: helen.mcshane{at}ndm.ox.ac.uk

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 of MVA85A was 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 IFN 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- and IL-2 response that was durable for 52 weeks. The magnitude of IFN- response was comparable to previous trials of MVA85A in bacillus Calmette-Guérin–vaccinated individuals. Antigen 85A–specific polyfunctional CD4⁺ T cells were detectable prior to vaccination with statistically significant increases in cell numbers after vaccination.

Conclusions: MVA85A is safe and highly immunogenic in individuals with LTBI. These results will facilitate further trials in TB-endemic areas.

Clinical trial registered with www.clinicaltrials.gov (NCT00456183).

Key Words: human • latent TB • vaccine • Koch

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject MVA85A is the first new vaccine to be evaluated in Mycobacterium tuberculosis latently infected subjects. What This Study Adds to the Field MVA85A is safe and highly immunogenic in individuals with LTBI. These results will facilitate further trials in TB-endemic areas.

 

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