Dr Cristian Segura-Cerda, CIATEJ - VALIDATE Fellow
Evaluation of the efficacy of BCGΔBCG1419c vaccination plus a booster of EsxG/EsxH-derived peptides to prevent tuberculosis progression caused by Mycobacterium tuberculosis strains prevalent in Latin America
The current global burden of tuberculosis makes it necessary to count on an efficacious vaccine that would be able to prevent infection by the harmful bacteria Mycobacterium tuberculosis (M. tuberculosis) and/or its progression to overt disease. An unmet challenge for new vaccines is how they protect against the variety of strains of M. tuberculosis which circulate around the world. In Latin America, two main lineages of M. tuberculosis strains have been recognized to circulate in the continent. These lineages, also present in Europe and Asia, differ in how tuberculosisis presents in the body. Ideally, a new vaccine against tuberculosis should generate protection against a broad variety of M. tuberculosis strains to have the greatest impact on health.
In this project, a vaccination strategy is proposed to improve the protection against this diversity of M. tuberculosis strains. It comprises the administration of the vaccine candidate BCGΔBCG1419c, which has been shown to be effective in reducing progression of tuberculosis in experimental models, particularly by conferring protection against chronic disease. This strain produces more biofilms in vitro than BCG, a form of growth which is common among diverse lineages of M. tuberculosis strains. Intranasal adminstration of EsxG/EsxH-derived peptides is proposed to boost protection. EsxG and EsxH participate in the acquisition of iron and zinc, minerals essential for mycobacterial metabolism. EsxG and EsxH are highly conserved in clinical strains from different lineages. Peptides derived from the structure of EsxG/EsxH have shown to induce higher titers of IgG class antibodies with a direct lysing effect against mycobacteria and to confer protection against tuberculosis in mice. This system has the potential to produce immunity in a systemic and a local way, then providing a broader spectrum of protection against strains which represent the variety of mycobacteria present in Latin America.
Find out more about Dr Cristian Segura-Cerda here.