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Hyper-attenuated MTBVAC erp mutant protects against tuberculosis in mice.

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 erp(-), 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 erp(-) strain did not compromise its protective efficacy profile in comparison with BCG. These results postulate MTBVAC erp(-) 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.

journal_name

Vaccine

journal_title

Vaccine

authors

Solans L,Uranga S,Aguilo N,Arnal C,Gomez AB,Monzon M,Badiola JJ,Gicquel B,Martin C

doi

10.1016/j.vaccine.2014.07.047

subject

Has Abstract

pub_date

2014-09-08 00:00:00

pages

5192-7

issue

40

eissn

0264-410X

issn

1873-2518

pii

S0264-410X(14)00990-6

journal_volume

32

pub_type

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