title: 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.
authors: Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, C/Domingo Miral s/n, 50009 Zaragoza, Spain; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
authors: Luis
authors: L
authors: Solans
authors: Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, C/Domingo Miral s/n, 50009 Zaragoza, Spain; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
authors: Santiago
authors: S
authors: Uranga
authors: Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, C/Domingo Miral s/n, 50009 Zaragoza, Spain; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
authors: Nacho
authors: N
authors: Aguilo
authors: Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, C/Domingo Miral s/n, 50009 Zaragoza, Spain; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
authors: Carmen
authors: C
authors: Arnal
authors: Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, C/Domingo Miral s/n, 50009 Zaragoza, Spain; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
authors: Ana Belen
authors: AB
authors: Gomez
authors: Research Centre for Encephalopathies and Transmissible Emerging Diseases, Universidad de Zaragoza, Zaragoza, Spain.
authors: Marta
authors: M
authors: Monzon
authors: Research Centre for Encephalopathies and Transmissible Emerging Diseases, Universidad de Zaragoza, Zaragoza, Spain.
authors: Juan Jose
authors: JJ
authors: Badiola
authors: Institute Pasteur, Mycobacterial Genetics, 25-28 Rue du Docteur Roux, 75015 Paris, France.
authors: Brigitte
authors: B
authors: Gicquel
authors: Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, C/Domingo Miral s/n, 50009 Zaragoza, Spain; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; Servicio de Microbiología, Hospital Universitario Miguel Servet, ISS Aragón, Paseo Isabel la Católica 1-3, 50009 Zaragoza, Spain. Electronic address: carlos@unizar.es.
authors: Carlos
authors: C
authors: Martin
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics*; D002460:Cell Line; D004195:Disease Models, Animal; D008565:Membrane Proteins / Q000235:genetics*; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D001500:BCG Vaccine; D001426:Bacterial Proteins; C096737:ERP protein, Mycobacterium tuberculosis; D008565:Membrane Proteins; D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated
keywords: Live-attenuated vaccines; MTBVAC; Tuberculosis vaccines