Abstract
SummaryIn 2015, there were an estimated 10.4 million new tuberculosis (TB) cases and 1.4 million deaths worldwide. Bacille Calmette–Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the vaccine available against TB, but it is insufficient for global TB control. This study evaluated the immunogenicity of the Mycobacterium tuberculosis antigen Rv1626 in mice while assessing the effect of co‐delivering either Cpe30 (immunostimulatory peptide), CS.T3378–395 (promiscuous T helper epitope) or flagellin (TLR5 agonist) or a combination of all three immunostimulatory agents. Rv1626 and the respective immunostimulatory proteins/peptides were co‐displayed on polyhydroxybutyrate beads assembled inside an engineered endotoxin‐free mutant of Escherichia coli. Mice vaccinated with these beads produced immune responses biased towards Th1‐/Th17‐type responses, but inclusion of Cpe30, CS.T3378–395 and flagellin did not enhance immunogenicity of the Rv1626 protein. This was confirmed in a M. bovis challenge experiment in mice, where Rv1626 beads reduced bacterial cell counts in the lungs by 0.48 log10 compared with the adjuvant alone control group. Co‐delivery of immunostimulatory peptides did not further enhance protective immunity.
Highlights
Polyhydroxyalkanoates (PHAs) are biopolyesters naturally produced as intracellular inclusions by many bacteria and archaea
The knowledge about topology, structure and properties of PhaC, which remains covalently linked to the PHB granules, has allowed translational fusion of foreign proteins to produce functionalized beads. These beads have been used for biomedical applications like protein production and purification as well as diagnostics and vaccines (Parlane et al, 2016; Rehm et al, 2016)
For splenocytes stimulated with PPDB, Bacille Calmette–Guerin (BCG) vaccination induced significantly higher levels of IFN-c than the negative control and higher IL-4 than all the other groups
Summary
Polyhydroxyalkanoates (PHAs) are biopolyesters naturally produced as intracellular inclusions by many bacteria and archaea. PHB beads displaying Ag85A-ESAT-6 antigens from Mycobacterium tuberculosis induced stronger humoral and cellular immune responses than vaccination with soluble Ag85A-ESAT-6 (Grage et al, 2009) and resulted in protection against Mycobacterium bovis challenge (Parlane et al, 2012). Serum IgG1 and IgG2c responses to Rv1626 in mice vaccinated with Rv1626 beads with or without addition of immunomodulators were evaluated by ELISA (Fig. S2).
Sign-in/Register to view highlights & summary 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.
