title: Vesicular Stomatitis Virus-Vectored Multi-Antigen Tuberculosis Vaccine Limits Bacterial Proliferation in Mice following a Single Intranasal Dose.
abstract: Tuberculosis (TB) remains a serious health problem worldwide, and an urgent need exists to improve or replace the available vaccine,Mycobacterium bovisbacillus Calmette-Guérin (BCG). Most vaccination protocols adapt two or three doses to induce long-term lasting immunity. Our previous study showed that the naked DNA encoding the triple-antigen fusion TFP846 (Rv3615c-Mtb10.4-Rv2660c) induced robust T cellular immune responses accompanying four inoculations against mycobacteria infection. However, a number of compliance issues exist in some areas lacking the appropriate medical infrastructure with multiple administrations. In this study, a novel vesicular stomatitis virus expressing TFP846 (VSV-846) was developed and the immune responses elicited by VSV-846 were evaluated. We observed that intranasal delivery of VSV-846 induced a potent antigen-specific T cell response following a single dose and VSV-846 efficiently controlled bacterial growth to levels ~10-fold lower than that observed in the mock group 6 weeks post-infection in BCG-infected mice. Importantly, mice immunized with VSV-846 provided long-term protection against mycobacteria infection compared with those receiving p846 or BCG immunization. Increased memory T cells were also observed in the spleens of VSV-846-vaccinated mice, which could be a potential mechanism associated with long-term protective immune response. These findings supported the use of VSV as an antigen delivery vector with the potential for TB vaccine development.
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity Institutes of Biology and Medical Sciences, Soochow University Suzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity Institutes of Biology and Medical Sciences, Soochow University Suzhou, China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Dong
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity Institutes of Biology and Medical Sciences, Soochow University Suzhou, China.
authors.forename: Sidong
authors.initials: S
authors.lastname: Xiong
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D001500:BCG Vaccine / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D007111:Immunity, Cellular; D007371:Interferon-gamma; D008168:Lung / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000276:immunology; D013154:Spleen; D014376:Tuberculosis / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000008:administration & dosage*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology; D018116:Vesiculovirus; D014760:Viral Fusion Proteins; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D000956:Antigens, Viral; D001500:BCG Vaccine; D032581:Tuberculosis Vaccines; D014614:Vaccines, Synthetic; D014760:Viral Fusion Proteins; D014765:Viral Vaccines; D007371:Interferon-gamma
keywords: mycobacteria; tuberculosis; vaccine; vesicular stomatitis virus