The use of Streptomyces for immunization against mycobacterial infections

Autor: Arzuaga, Nesty Olivares, Vila Granda, Ailin, Gómez, Juan Carlos Ramírez, San Miguel, María Elena Sarmiento García, Bourzac, Juan Francisco Infante, Hernández, Yamilé López, Elías López, Ana Lucrecia, Pólux, Carlos Román Vallín, Mesa, Leonora González, Hernández-Pando, Rogelio, Domínguez, Armando Acosta
Zdroj: Human Vaccines; September 2011, Vol. 7 Issue: 9 p934-940, 7p
Abstrakt: Tuberculosis is one of the leading causes of mortality produced by an infectious agent. Different strategies including bioinformatics are currently being tested to identify and improve vaccines against tuberculosis. Comparative genome analysis between Streptomyces coelicolorand Mycobacterium tuberculosissuggest that both descend from a common Actinomycete ancestor. In this work, we suggest the use of Streptomyces as a live vector and explore the capacity of Streptomyces immunization to induce a protective response against mycobacterial infection. First, we compared the theoretical proteomes of S. coelicolor A3(2) with those of M. tuberculosisH37Rv and Mycobacterium bovisAF2122/97. This study showed a high similarity at the level of individual genes sequences with both bacteria sharing several membrane proteins. Then, we administered Streptomyces intraperitoneally to mice and determined its distribution by histopathology and culture; we did not find systemic dissemination. After administration of Streptomyces through different routes, we identified the most immunogenic, inducing strong humoral response, as denoted by the high serum antibody titers against this organism with cross reactivity to mycobacterial antigens. Finally, we evaluated the level of protection elicited by the inoculation of Streptomyces in Balb/c mice challenged with BCG. In these animals, lung bacillary loads were significantly lower than the control non-sensitized group.. These observations, along with Streptomyces’ potential for expressing foreign proteins, suggest that Streptomyces could be an advantageous vector in the design of new tuberculosis vaccines.
Databáze: Supplemental Index