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: Vanessa Bastos Pereira, Tessália Diniz Luerce Saraiva, Bianca Mendes Souza, Meritxell Zurita-Turk, Marcela Santiago Pacheco Azevedo, Camila Prósperi De Castro, Pamela Mancha-Agresti, Janete Soares Coelho Dos Santos, Ana Cristina Gomes Santos, Ana Maria Caetano Faria, Sophie Leclercq, Vasco Azevedo, Anderson Miyoshi
• Journal: Applied microbiology and biotechnology (Appl Microbiol Biotechnol) Vol. 99 Issue 4 Pg. 1817-26 (Feb 2015) ISSN: 1432-0614 [Electronic] Germany
• PMID: 25503506 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Bacterial
• Bacterial Proteins
• Drug Carriers
• ESAT-6 protein, Mycobacterium tuberculosis
• Immunoglobulin A, Secretory
• Tuberculosis Vaccines
• Vaccines, DNA
• Vaccines, Synthetic
• Interferon-gamma

Topics

• Animals
• Antigens, Bacterial (genetics, immunology)
• Bacterial Proteins (genetics, immunology)
• Cloning, Molecular
• Colon (immunology)
• Drug Carriers
• Feces (chemistry)
• Immunoglobulin A, Secretory (analysis)
• Interferon-gamma (metabolism)
• Lactococcus lactis (genetics)
• Leukocytes, Mononuclear (immunology)
• Mice, Inbred BALB C
• Mycobacterium tuberculosis (genetics, immunology)
• Plasmids
• Spleen (immunology)
• Tuberculosis Vaccines (administration & dosage, genetics, immunology, isolation & purification)
• Vaccines, DNA (administration & dosage, genetics)
• Vaccines, Synthetic (administration & dosage, genetics, immunology, isolation & purification)