Bioengineering a bacterial pathogen to assemble its own particulate vaccine capable of inducing cellular immunity

Abstract

Many bacterial pathogens naturally form cellular inclusions. Here the immunogenicity of polyhydroxyalkanoate (PHA) inclusions and their use as particulate vaccines delivering a range of host derived antigens was assessed. Our study showed that PHA inclusions of pathogenic Pseudomonas aeruginosa are immunogenic mediating a specific cell-mediated immune response. Protein engineering of the PHA inclusion forming enzyme by translational fusion of epitopes from vaccine candidates outer membrane proteins OprI, OprF, and AlgE mediated self-assembly of PHA inclusions coated by these selected antigens. Mice vaccinated with isolated PHA inclusions produced a Th1 type immune response characterized by antigen-specific production of IFN-γ and IgG2c isotype antibodies. This cell-mediated immune response was found to be associated with the production of functional antibodies reacting with cells of various P. aeruginosa strains as well as facilitating opsonophagocytic killing. This study showed that cellular inclusions of pathogenic bacteria are immunogenic and can be engineered to display selected antigens suitable to serve as particulate subunit vaccines against infectious diseases.

Understanding Pseudomonas aeruginosa–Host Interactions: The Ongoing Quest for an Efficacious Vaccine

“…Influenza virus [278], cowpea mosaic virus [279,280], tobacco mosaic virus [281] and adenovirus [282][283][284][285] were used as vectors. Finally, a polyhydroxyalkanoate (PHA) nano-vaccine with P. aeruginosa cellular inclusions engineered to display OprF, OprI and AlgE antigens in the surface induced a protective Th1-cellular response associated with the production of antibodies that reacted with different strains and possessed opsonophagocytic killing activity [158].…”

Bioengineered polyester beads co-displaying protein and carbohydrate-based antigens induce protective immunity against bacterial infection

“…Antigen-displaying PHB beads were also produced in other bacterial hosts such as Mycobacterium smegmatis and Lactococcus lactis 25 , 32 . In a recent study, the bacterial pathogen’s own polyhydroxyalkanoate inclusion assembly was engineered to produce antigen-displaying particulate vaccines 33 .…”

Polymeric nanoparticle vaccines to combat emerging and pandemic threats

“…vaccination. [ 138 ] PHB-core protein-shell particle Fusion antigenic epitopes AlgE, OprF and OprI Alum s.c. Mouse IgG1 and IgG2c, with opsonophagocytic antibody titer Th1 N/E Without the adjuvant, Th1 immune response can be induced [ 156 ] Streptococcus pneumoniae cCHP nanogel PspA – i.n. Rhesus Macaque PspA-specific bronchoalveolar fluid IgG and nasal wash IgA antibodies, with neutralizing antibody titer Th2 and Th17 N/E The mice injected intraperitoneally with the pooled sera of macaques nasally immunized with the nanogels were protected from the challenge for at least 2 weeks [ 157 ] PHB-core protein-shell particle Ply and 19F CPS – s.c. Mouse IgG with the dominant IgG1 and IgG2b, and opsonophagocy-tic antibody titer Th2 N/E The IgG was persistent for up to 6 months and recognized Ply in whole cell lysates of six different S. pneumoniae serotypes [ 158 ] PHB-core protein-shell particle PsaA – s.c. Mouse IgG with the dominant IgG1 and IgG2b Th2 N/E The elicited IgG recognized PsaA in whole cell lysate of seven different serotypes of S. pneumoniae [ 159 ] Neisseria meningtidis PHB-core protein-shell particle NadA and MenC ...…”