Lessons from the first clinical trial of a non-licensed vaccine among Ugandan adolescents: a phase II field trial of the tuberculosis candidate vaccine, MVA85A

Abstract

Background: A more effective vaccine for tuberculosis (TB) is a global public health priority. Vaccines under development will always need evaluation in endemic settings, most of which have limited resources. Adolescents are an important target population for a new TB vaccine and for other vaccines which are relevant at school-age. However, in most endemic settings there is limited experience of trials of investigational products among adolescents, and adolescents are not routinely vaccinated. Methods: We used Modified vaccinia Ankara-expressing Ag85A (MVA85A), a well-tolerated candidate vaccine for tuberculosis, to assess the effect of Schistosoma mansoni infection on vaccine immunogenicity among Ugandan adolescents in primary school. We describe here the challenges and lessons learned in designing and implementing this first clinical trial among Ugandan adolescents using a non-licensed vaccine. Results: The school based immunization study was feasible and adhered to Good Clinical Practice principles. Engagement with the community and all stakeholders was critical for successful implementation of the trial. Creative and adaptable strategies were used to address protocol-specific, operational and logistical challenges. This study provided lessons and solutions that can be applied to other trials among adolescents in similar settings elsewhere, and to school-based immunization programs. Conclusion: Sufficient time and resources should be planned for community preparation and sensitization to ensure buy in and acceptance of a project of this kind. This trial shows that challenges to implementing early field trials in Africa are not insurmountable and that necessary well-planned high-quality ethical trials are feasible and should be encouraged. Trial Registration: ClinicalTrials.gov NCT02178748 03/06/2014

The TB vaccine clinical trial centre directory: an inventory of clinical trial centres in sub-Saharan Africa

“…Thus, further work should also investigate what incentivises institutions to become a TB vaccine trial centre. For example, prior evaluations of TB vaccine trial centres indicated that difficulties with logistics and operations could pose a problem in terms of trial execution (9,10). Kaguthi et al (11) discuss lessons learned from development of a TB vaccine trial centre for design and implementation of trials in Africa.…”

Metabolic Programming of Macrophages: Implications in the Pathogenesis of Granulomatous Disease

“…Furthermore, it was recently shown that infection with S. haematobium induces long-term, persistent epigenetic alterations resulting in a weakened inflammatory response and increased susceptibility to tuberculosis (251). Hence, research on tuberculosis therapies and vaccine candidates has made a point to assess the effect of Schistosoma species on tuberculosis disease progression (252). As both pathogens form granulomas but affect macrophage metabolism in a vastly different manner, it would be interesting to analyze granuloma formation in co-infection settings, particularly with regard to lipid metabolism.…”