title: Development of a new DNA vaccine based on mycobacterial ESAT-6 antigen delivered by recombinant invasive Lactococcus lactis FnBPA+.
abstract: The use of the food-grade bacterium Lactococcus lactis as a vehicle for the oral delivery of DNA vaccine plasmids constitutes a promising strategy for vaccination. The delivery of DNA plasmids into eukaryotic cells is of critical importance for subsequent DNA expression and effectiveness of the vaccine. In this context, the use of the recombinant invasive L. lactis FnBPA+ (fibronectin-binding protein A) strain for the oral delivery of the eukaryotic expression vector vaccination using lactic acid bacteria (pValac), coding for the 6-kDa early secreted antigenic target (ESAT-6) gene of Mycobacterium tuberculosis, could represent a new DNA vaccine strategy against tuberculosis. To this end, the ESAT-6 sequence was cloned into the pValac vector; the L. lactis fibronectin-binding protein A (FnBPA)+ (pValac:ESAT-6) strain was obtained, and its immunological profile was checked in BALB/c mice. This strain was able to significantly increase interferon gamma (IFN-γ) production in spleen cells, showing a systemic T helper 1 (Th1) cell response. The mice also showed a significant increase in specific secretory immunoglobulin A (sIgA) production in colon tissue and fecal extracts. Thus, this is the first time that L. lactis has been used to deliver a plasmid DNA harboring a gene that encodes an antigen against tuberculosis through mucous membranes.
authors.affiliation: Laboratório de Genética Celular e Molecular, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, 31270-901, Brazil.
authors.forename: Vanessa Bastos
authors.initials: VB
authors.lastname: Pereira
authors.forename: Tessália Diniz Luerce
authors.initials: TD
authors.lastname: Saraiva
authors.forename: Bianca Mendes
authors.initials: BM
authors.lastname: Souza
authors.forename: Meritxell
authors.initials: M
authors.lastname: Zurita-Turk
authors.forename: Marcela Santiago Pacheco
authors.initials: MS
authors.lastname: Azevedo
authors.forename: Camila Prósperi
authors.initials: CP
authors.lastname: De Castro
authors.forename: Pamela
authors.initials: P
authors.lastname: Mancha-Agresti
authors.forename: Janete Soares Coelho
authors.initials: JS
authors.lastname: Dos Santos
authors.forename: Ana Cristina Gomes
authors.initials: AC
authors.lastname: Santos
authors.forename: Ana Maria Caetano
authors.initials: AM
authors.lastname: Faria
authors.forename: Sophie
authors.initials: S
authors.lastname: Leclercq
authors.forename: Vasco
authors.initials: V
authors.lastname: Azevedo
authors.forename: Anderson
authors.initials: A
authors.lastname: Miyoshi
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D003001:Cloning, Molecular; D003106:Colon / Q000276:immunology; D004337:Drug Carriers; D005243:Feces / Q000737:chemistry; D007071:Immunoglobulin A, Secretory / Q000032:analysis; D007371:Interferon-gamma / Q000378:metabolism; D013294:Lactococcus lactis / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D010957:Plasmids; D013154:Spleen / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004337:Drug Carriers; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007071:Immunoglobulin A, Secretory; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D007371:Interferon-gamma