Abstract
ABSTRACTMycobacterium bovis BCG is the only available vaccine for protection against tuberculosis (TB). While BCG protects children from severe disease, it has little impact on pulmonary disease in adults. A recombinant BCG vaccine BCG ΔureC::hly (strain VPM1002) is in advanced clinical trials and shows promise for improved vaccine safety but little change in efficacy in animal models. A second-generation recombinant BCG vaccine with an additional deletion of the nuoG gene (BCG ΔureC::hly ΔnuoG) shows improved efficacy in a mouse model compared to that of VPM1002. BCG was first used in humans in 1921 and, like Sleeping Beauty pricked by the spinning wheel, we have slept for 100 years, showing a reluctance to invest in clinical development or in biomanufacturing capacity for TB vaccines. The advance of recombinant BCGs should awaken us from our sleep and call us to invest in new-generation TB vaccines and to protect the biomanufacture of our current BCG vaccine.
Highlights
2 million people die each year of tuberculosis (TB), and an estimated one-third of the world’s population is infected with Mycobacterium tuberculosis [1]
The risk of disseminated disease due to uncontrolled replication of the current Bacille Calmette-Guérin (BCG) vaccine is higher in HIV-exposed infants, and BCG is not recommended in this population
If BCG ⌬ureC::hly ⌬nuoG is more effective than VPM1002, what are the implications for the current clinical development of VPM1002? BCG was first used as a human vaccine in 1921 and, like Sleeping Beauty pricked by the spinning wheel, we have slumbered for 100 years, depending on BCG alone for protection
Summary
2 million people die each year of tuberculosis (TB), and an estimated one-third of the world’s population is infected with Mycobacterium tuberculosis [1]. New TB vaccines seek to improve protection against TB either by increasing the magnitude of the CD4 T cell response induced by BCG or by broadening the immune response, for example, through the induction of a CD8 T cell response. In early-phase clinical trials, the CD4ϩ and CD8ϩ antigen-specific responses to VPM1002 did not differ from those induced by BCG, there was early enhancement of purified protein derivative (PPD)-specific antibodies [11].
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