Abstract
BackgroundTuberculosis is one of the most common and deadliest infectious diseases worldwide affecting almost a third of the world’s population. Although this disease is being prevented and controlled by the Bacille Calmette Guérin (BCG) vaccine, the protective efficacy is highly variable and substandard (0–80%) in adults. Therefore, novel and effective tuberculosis vaccine that can overcome the limitations from BCG vaccine need to be developed.ResultsA novel approach of utilizing an in-trans protein surface display system of Lactobacillus plantarum carrying and displaying combination of Mycobacterium tuberculosis subunit epitope antigens (Ag85B, CFP-10, ESAT-6, Rv0475 and Rv2031c) fused with LysM anchor motif designated as ACERL was constructed, cloned and expressed in Esherichia coli Rossetta expression host. Subsequently the binding capability of ACERL to the cell wall of L. plantarum was examined via the immunofluorescence microscopy and whole cell ELISA where successful attachment and consistent stability of cell wall binding up to 4 days was determined. The immunization of the developed vaccine of L. plantarum surface displaying ACERL (Lp ACERL) via the oral route was studied in mice for its immunogenicity effects. Lp ACERL immunization was able to invoke significant immune responses that favor the Th1 type cytokine response of IFN-γ, IL-12 and IL-2 as indicated by the outcome from the cytokine profiling of spleen, lung, gastrointestinal tract (GIT), and the re-stimulation of the splenocytes from the immunized mice. Co-administration of an adjuvant consisting of Lactococcus lactis secreting mouse IL-12 (LcIL-12) with Lp ACERL was also investigated. It was shown that the addition of LcIL-12 was able to further generate significant Th1 type cytokines immune responses, similar or better than that of Lp ACERL alone which can be observed from the cytokine profiling of the immunized mice’s spleen, lung and GIT.ConclusionsThis study represents a proof of concept in the development of L. plantarum as a carrier for a non-genetically modified organism (GMO) tuberculosis vaccine, which may be the strategy in the future for tuberculosis vaccine development.
Highlights
Tuberculosis is one of the most common and deadliest infectious diseases worldwide affecting almost a third of the world’s population
The novelty of the present study lies in the application of the in-trans surface display concept where the non-covalently anchor protein of Lysin motif (LysM) domain was fused to the recombinant M. tuberculosis
The combined results from these studies showed that the candidate vaccine of L. plantarum Pa21 (Lp) L. plantarum ACERL (ACERL) had the potential for the rational development and design of effective mucosal tuberculosis vaccine which targets the oral route for vaccine administration
Summary
Tuberculosis is one of the most common and deadliest infectious diseases worldwide affecting almost a third of the world’s population. The growing interest in the use of the LAB protein surface display system for mucosal vaccination purposes is due to strong requirement for effective strategies in delivering vaccine antigens, microbiocides and therapeutics to the mucosal tissues [7] in which the M. tuberculosis infection target entry site is at the mucosal lining of the respiratory tract By focusing on this route for vaccine administration, effective protection gain by the mucosal cells against the pathogen can be achieved primarily by the enhancement of mucosal cells to vaccine interaction whilst having reduced potential side effects when compared to systemic routes of administration [8]. This is because studies have shown that protection against mycobacterial infection were conferred by mucosal immunity that induces both mycobacterial-specific T helper cells-1 (Th-1) and secretory IgA responses which are the key immune response against M. tuberculosis [9, 10]
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