Innovative antigen carrier system for the development of tuberculosis vaccines

Abstract

A major obstacle to tuberculosis (TB)‐subunit–vaccine development has been the induction of inadequate levels of protective immunity due to the limited breadth of antigen in vaccine preparations. In this study, immunogenic mycobacterial fusion peptides Ag85B‐TB10.4 and Ag85B‐TB10.4‐Rv2660c were covalently displayed on the surface of self‐assembled polyester particles. This study investigated whether polyester particles displaying mycobacterial antigens could provide augmented immunogenicity (i.e., offer an innovative vaccine formulation) when compared with free soluble antigens. Herein, polyester particle–based particulate vaccines were produced in an endotoxin‐free Escherichia coli strain and emulsified with the adjuvant dimethyl dioctadecyl ammonium bromide. C57BL/6 mice were used to study the immunogenicity of formulated particulate vaccines. The result of humoral immunity showed the antibodies only interacted with target antigens and not with PhaC and the background proteins of the production host. The analysis of T helper 1 cellular immunity indicated that a relatively strong production of cellular immunity biomarkers, IFN‐γ and IL‐17A cytokines, was induced by particulate vaccines when compared with the respective soluble controls. This study demonstrated that polyester particles have the potential to perform as a mycobacterial antigen–delivery agent to induce augmented antigen‐specific immune responses in contrast to free soluble vaccines.—Chen, S., Sandford, S., Kirman, J. R., Rehm, B. H. A. Innovative antigen carrier system for the development of tuberculosis vaccines. FASEB J. 33, 7505–7518 (2019). http://www.fasebj.org

A Pseudomonas aeruginosa-Derived Particulate Vaccine Protects against P. aeruginosa Infection

“…This study utilized the inherent PHA synthesis capability of P. aeruginosa to manufacture its own empty PHA beads and PHA beads coated with selected antigens as particulate vaccine candidates. P. aeruginosa is one of the many bacteria that produce PHA inclusions for carbon and energy storage [ 58 ]. Vaccine candidate antigens/epitopes were engineered to coat the PHA beads during in vivo assembly and a downstream process was devised to retain associated HCPs as well as the polysaccharide Psl, another candidate vaccine antigen.…”

Particulate Mycobacterial Vaccines Induce Protective Immunity against Tuberculosis in Mice

“…An endotoxin free strain, ClearColi BL21(DE3), was used as the host for nanoparticle production. The methods of producing polyester nanoparticles and protein nanoparticles in ClearColi BL21(DE3) were previously described [ 20 , 21 ]. In particular, PhaA, PhaB and PhaC are the three key enzymes required for the formation of polyester nanoparticles.…”

“…Bacterial cells harboring various particulate vaccines were disrupted using a microfluidizer (Microfluidics; Westwood, MA, USA) and purified by centrifugation through successive washing. The isolation, purification and sterilization procedures of nanoparticle vaccines have been described previously [ 20 , 21 ].…”

“…The splenocyte restimulation was described previously [ 20 , 21 ]. Briefly, 100 μL of single spleen cells suspensions (at a concentration of 5 × 10 6 per mL, diluted with complete RPMI media) were loaded to U-bottomed 96-well plates (Life Technologies; USA).…”

“…We previously showed that these two mycobacterial antigen fusions, H4 and H28, can be engineered to self-assemble into various particulate mycobacterial vaccines (polyester nanoparticle-H4, polyester nanoparticle-H28, H4 nanoparticles and H28 nanoparticles) in E. coli cells. These particulate mycobacterial vaccines showed increased immunogenicity with respect to antibody responses and cell-mediated immunity in mice when compared to their soluble counter parts [ 20 , 21 ]. We have investigated whether the mycobacterial fusions H4 and/or H28 delivered as defined polyester or protein nanoparticles could induce protective immunity in a mouse model of aerosol M. tuberculosis infection.…”