A phase I safety study of TB vaccine candidate MTBVAC, the first live-attenuated Mycobacterium tuberculosis-based vaccine to enter clinical trials, shows very good results in the first intermediate analysis. Although the study is not finished yet, the 36 volunteers did not show any signs of disease or side effects so far. “In my experience, it is one of the safest vaccines ever tested,” says Professor François Spertini of the University Hospital of Lausanne (CHUV) in Switzerland, the Principal Investigator of the trial. “But a further nine months of investigation is necessary to further validate safety and ascertain whether the vaccine is also effective.”
Present vaccine BCG is based on attenuated strain of Mycobacterium bovis isolated from cows. MTBVAC, developed by Professor Carlos Martin of the University of Zaragoza, is a live vaccine based on attenuated M. tuberculosis isolated from humans; a strongly weakened version of the bacterium that causes TB and the first candidate of this kind ever tested in humans. Made harmless in the laboratory, the vaccine stimulates the human immune system to recognise, and eventually prevent, TB disease. Pre-clinical studies showed great promise. If MTBVAC successfully runs through all phases of clinical evaluation and shows to be more effective, it could replace BCG and protect millions of children and adults from getting tuberculosis.
Last January François Spertini, who has extensive experience in clinical trials with vaccines, started a Phase I study in Lausanne. Thirty-six healthy volunteers participated in order to ensure the safety and immunogenicity of the vaccine candidate MTBVAC. The participants were divided into three groups depending on the dose which has been administered (1,000 or 10,000 or 100,000 units of MTBVAC). In the first two cohorts, seven months after the monitoring period considered necessary to confirm possible side effects or disease infection, the vaccine has been shown to be safe. The last dose of the latter group was administered on 6 November and so far no safety issues occurred. Possible side effects or disease generally occurs in the first days after vaccination, so this first positive signal is very promising.
According to Professor Spertini, who has worked on many vaccine trials, this is one of the safest he has seen. But he also emphasized that we’re not there yet. A second objective of the study was to test the immunogenicity, which may give indications on the potential protective value of the vaccine. Six more months will be necessary to analyse these results. If the immune response is also good, the vaccine may progress to the next clinical study in South Africa, where tuberculosis is endemic. In that case, the current sponsors Biofabri and TBVI said they were committed to further sponsor and to help find the additional needed financial resources.
The development of MTBVAC has been made possible through a unique European collaboration and was financed by the European Commission through TBVI, Biofabri – a Spanish biopharmaceutical company – and the Spanish Government. The project started with Professor Brigitte Gicquel at Institute Pasteur in Paris, in collaboration with Professor Carlos Martin of the University of Zaragoza, where the actual vaccine was constructed. Pre-clinical development involved various partners of TBVI Throughout the process, TBVI’s special expert teams have provided scientific support and developmental expertise.
Source: TBVI