Safety and Immunogenicity of the Candidate Tuberculosis Vaccine MVA85A in West Africa

Abstract

BackgroundVaccination with a recombinant modified vaccinia Ankara expressing antigen 85A from Mycobacterium tuberculosis, MVA85A, induces high levels of cellular immune responses in UK volunteers. We assessed the safety and immunogenicity of this new vaccine in West African volunteers.Methods and FindingsWe vaccinated 21 healthy adult male subjects (11 BCG scar negative and 10 BCG scar positive) with MVA85A after screening for evidence of prior exposure to mycobacteria. We monitored them over six months, observing for clinical, haematological and biochemical adverse events, together with assessment of the vaccine induced cellular immune response using ELISPOT and flow cytometry. MVA85A was well tolerated with no significant adverse events. Mild local and systemic adverse events were consistent with previous UK trials. Marked immunogenicity was found whether individuals had a previous BCG scar or not. There was not enhanced immunogenicity in those with a BCG scar, and induced T cell responses were better maintained in apparently BCG-naïve Gambians than previously studied BCG-naïve UK vaccinees. Although responses were predominantly attributable to CD4+ T cells, we also identified antigen specific CD8+ T cell responses, in subjects who were HLA B-35 and in whom enough blood was available for more detailed immunological analysis.ConclusionsThese data on the safety and immunogenicity of MVA85A in West Africa support its accelerated development as a promising booster vaccine for tuberculosis.Trial RegistrationClinicalTrials.gov NCT00423839

Differential Cytokine Levels in Adults Induced by a Novel Candidate TB Boost Vaccine, MVA85A-According to Previous BCG Vaccination Status

“…We have previously reported that vaccination with MVA85A induces comparable immune responses to Antigen 85A and PPD regardless of BCG status in Gambian adult subjects [7]. In contrast BCG scar positive subjects from the United Kingdom mounted a higher response to BCG naïve subjects suggesting the threshold of responses is affected by environmental mycobacteria [6].…”

“…MVA85A was safe well tolerated and immunogenic when administered to adult volunteers in the UK, The Gambia and South Africa [6][7][8]. Interestingly, in The Gambian study, the immunogenicity of MVA85A in BCG vaccinated (BCG+) and BCG naive (BCG-) adults was comparable, in contrast to studies in the UK where immunogenicity was higher in BCG vaccinated subjects [6].…”

“…This study was conducted between 2003 and 2005 and the setting and inclusion/exclusion criteria have been previously described [7]. 10 subjects with a visible BCG scar (an indicator of BCG vaccination status for BCG [7]) and another 11 without evidence of a scar of BCG vaccination were included in the study.…”

“…10 subjects with a visible BCG scar (an indicator of BCG vaccination status for BCG [7]) and another 11 without evidence of a scar of BCG vaccination were included in the study. The groups did not differ significantly with respect to age, height, weight and Mantoux skin test and all subjects were HIV seronegative.…”

“…These findings suggest that MVA85A may boost cumulative mycobacterial exposure which is comprised of exposure to BCG, non-tuberculous mycobacteria and M.tb, and that the contribution of BCG to this cumulative mycobacterial exposure is less relevant in adults in TB endemic countries. To gain a better understanding of the relevance of baseline anti-mycobacterial immunity, we examined the cytokine and chemokine profiles in plasma obtained before and after MVA85A vaccination according to the presence or absence of a BCG scar in these healthy Gambian adults that have been previously reported [7].…”