H1- and H56- subunit vaccines against TB - an overview of the clinical development

Despite a very effective worldwide vaccination program, BCG vaccination has proven to be insufficient to provide protection against TB disease, and a better vaccine is urgently needed. Statens Serum Institut has developed two TB vaccine candidates, H1:IC and its improved successor H56:IC. Both candidates are currently being tested in human clinical trials although H1:IC development will end in 2014 as H56:IC program will take over. These vaccines candidates are intended to be used in adolescents and young adults, and are designed to be effective in both M. tuberculosis - uninfected and latently infected persons. Being a subunit vaccine, the H1 consists of a recombinant fusion protein of two secreted mycobacterial antigens, Ag85B and ESAT-6, and to this core H56 adds a third antigen - the latency antigen Rv2660c. Both vaccines are adjuvated with the IC31 adjuvant This presentation summarize results from preclinical studies in rodents and non-human primates to five clinical trials of the H1:IC and H56:IC vaccines. In preclinical studies, H56:IC provides superior protection against TB disease compared to BCG alone both pre- and post- infection with M.tb. In human trials, H1:IC has been shown to be safe and to induce long term immune responses characterized by T cells with sustained regenerative potential. Latest, this has been shown in HIV infected patients with latent infection in Tanzania and South Africa. Furthermore, a large dose- and schedule trial including 240 adolescents is currently ongoing in South Africa. Recently H56:IC proved similar safety and immunogenicity profile as H1:IC in a small first-in-man trial. These clinical data provides the groundwork for further clinical development of H56:IC.