Development of a new DNA vaccine based on mycobacterial ESAT-6 antigen delivered by recombinant invasive Lactococcus lactis FnBPA+

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 vacc...

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Bibliographic Details
Published in:Applied microbiology and biotechnology 2015-02, Vol.99 (4), p.1817-1826
Main Authors: Pereira, Vanessa Bastos, Saraiva, Tessália Diniz Luerce, Souza, Bianca Mendes, Zurita-Turk, Meritxell, Azevedo, Marcela Santiago Pacheco, De Castro, Camila Prósperi, Mancha-Agresti, Pamela, dos Santos, Janete Soares Coelho, Santos, Ana Cristina Gomes, Faria, Ana Maria Caetano, Leclercq, Sophie, Azevedo, Vasco, Miyoshi, Anderson
Format: Article
Language:English
Subjects:
Analysis
Animals
Antigens
Antigens, Bacterial - genetics
Antigens, Bacterial - immunology
Applied Genetics and Molecular Biotechnology
Bacteria
Bacterial Proteins - genetics
Bacterial Proteins - immunology
Biomedical and Life Sciences
Biotechnology
CD4-positive T-lymphocytes
Cloning, Molecular
colon
Colon - immunology
Deoxyribonucleic acid
DNA
DNA vaccines
Drug Carriers
E coli
eukaryotic cells
Feces - chemistry
genes
Genetic recombination
immunoglobulin A
Immunoglobulin A, Secretory - analysis
Immunology
interferon-gamma
Interferon-gamma - secretion
lactic acid bacteria
Lactococcus
Lactococcus lactis
Lactococcus lactis - genetics
Leukocytes, Mononuclear - immunology
Life Sciences
mice
Mice, Inbred BALB C
Microbial Genetics and Genomics
Microbiology
mucosa
Mycobacteria
Mycobacterium tuberculosis
Mycobacterium tuberculosis - genetics
Mycobacterium tuberculosis - immunology
Plasmids
Production processes
Proteins
recombinant vaccines
Spleen - immunology
splenocytes
Studies
Tuberculosis
Tuberculosis Vaccines - administration & dosage
Tuberculosis Vaccines - genetics
Tuberculosis Vaccines - immunology
Tuberculosis Vaccines - isolation & purification
vaccination
Vaccines
Vaccines, DNA - administration & dosage
Vaccines, DNA - genetics
Vaccines, Synthetic - administration & dosage
Vaccines, Synthetic - genetics
Vaccines, Synthetic - immunology
Vaccines, Synthetic - isolation & purification
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Description
Summary: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.
ISSN:0175-7598
1432-0614
DOI:10.1007/s00253-014-6285-3