Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10964466 | Vaccine | 2014 | 6 Pages |
Abstract
Safety of individuals at risk of immune suppression is an important concern for live vaccines. The new-generation tuberculosis vaccine candidate MTBVAC, a genetically engineered doubly attenuated Mycobacterium tuberculosis mutant with deletions in phoP and fadD26 virulence genes has demonstrated comparable safety in different relevant animal models and superior protection in mice as compared to the only currently licensed tuberculosis vaccine Mycobacterium bovis BCG. Here we describe the construction of a highly attenuated MTBVAC-based live vaccine by an additional gene inactivation generated in erp of MTBVAC. The gene product of erp is an exported repeated protein (Erp), a virulence factor described to be involved in intracellular replication of M. tuberculosis. The resultant strain, MTBVAC erpâ, was tested in severe combined immunodeficiency (SCID) mouse model showing to be severely attenuated when compared to BCG and MTBVAC. Experiments conducted in immunocompetent mice revealed that the hyper-attenuated profile observed with MTBVAC erpâ strain did not compromise its protective efficacy profile in comparison with BCG. These results postulate MTBVAC erpâ as a potential tuberculosis vaccine candidate for use in high-risk populations of immune suppression (e.g., due to HIV infection), where the use of BCG is not recommended.
Related Topics
Life Sciences
Immunology and Microbiology
Immunology
Authors
Luis Solans, Santiago Uranga, Nacho Aguilo, Carmen Arnal, Ana Belen Gomez, Marta Monzon, Juan Jose Badiola, Brigitte Gicquel, Carlos Martin,