Abstract
Tuberculosis (TB) remains a major threat throughout the world and in 2015 it caused the death of 1.4 million people. The Bacillus Calmette-Guérin is the only existing vaccine against this ancient disease; however, it does not provide complete protection in adults. New vaccines against TB are eminently a global priority. The use of bacteria as vehicles for delivery of vaccine plasmids is a promising vaccination strategy. In this study, we evaluated the use of, an engineered invasive Lactococcus lactis (expressing Fibronectin-Binding Protein A from Staphylococcus aureus) for the delivery of DNA plasmid to host cells, especially to the mucosal site as a new DNA vaccine against tuberculosis. One of the major antigens documented that offers protective responses against Mycobacterium tuberculosis is the Ag85A. L. lactis FnBPA+ (pValac:Ag85A) which was obtained and used for intranasal immunization of C57BL/6 mice and the immune response profile was evaluated. In this study we observed that this strain was able to produce significant increases in the amount of pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6) in the stimulated spleen cell supernatants, showing a systemic T helper 1 (Th1) cell response. Antibody production (IgG and sIgA anti-Ag85A) was also significantly increased in bronchoalveolar lavage, as well as in the serum of mice. In summary, these findings open new perspectives in the area of mucosal DNA vaccine, against specific pathogens using a Lactic Acid Bacteria such as L. lactis.
Highlights
Tuberculosis (TB) is a disease with a high incidence rates around the world that was directly responsible for the death of about 1.4 million people in 2015 and an additional 0.4 million among people co-infected with HIV (WHO, 2016).Bacillus Calmette-Guérin (BCG) is an attenuated form of Mycobacterium bovis that is the only licensed vaccine in use, which prevents TB in infants and in the disseminated disease
The Ag85A open reading frame (ORF) (1017 bp) (Gen Bank number 886132) was successfully cloned into the pValac vector (Table 1). This vector consists of an eukaryotic unit containing the cytomegalovirus promoter and the polyadenylation signal of the bovine growth hormone (BGH), and a prokaryotic portion containing the RepA/RepC replication origins for L. lactis and OriColE1 replication origin for E. coli and, as well as the chloramphenicol (Cm) resistance gene
The invasive L. lactis Fibronectin-binding protein A (FnBPA)+ strain was transformed with the pValac:Ag85A plasmid resulting in the recombinant invasive L. lactis FnBPA+ strain
Summary
Tuberculosis (TB) is a disease with a high incidence rates around the world that was directly responsible for the death of about 1.4 million people in 2015 and an additional 0.4 million among people co-infected with HIV (WHO, 2016).Bacillus Calmette-Guérin (BCG) is an attenuated form of Mycobacterium bovis that is the only licensed vaccine in use, which prevents TB in infants and in the disseminated disease. Lactococcus lactis Delivering Ag85A Antigen it has limitations to protect adolescents and adults against the pulmonary disease (Kaufmann, 2010; da Costa et al, 2015). Another bottleneck of this vaccine is the memory immunity generated which declines with the age (Vijayalakshmi et al, 1993; Kaufmann, 2004). It is well known that the main protective antigens of M. tuberculosis are secreted proteins of the culture filtrate Among these proteins Ag85A, B and C, which belong to the antigen 85 (Ag85) complex, have been reported to provide protection against TB (D’Souza et al, 2003; Jain et al, 2008). Ag85A stimulates IFN-γ production by peripheral blood mononuclear cells (PBMC) from both BCG-vaccinated (Anuradha et al, 2007, 2008) and TB patients (Priya et al, 2009)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
