Bioengineering a bacterial pathogen to assemble its own particulate vaccine capable of inducing cellular immunity.
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.
Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand.|AgResearch, Hopkirk Research Institute, Palmerston North, New Zealand.
Jason W
JW
Lee
AgResearch, Hopkirk Research Institute, Palmerston North, New Zealand.
Natalie A
NA
Parlane
AgResearch, Hopkirk Research Institute, Palmerston North, New Zealand.
D Neil
DN
Wedlock
Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand.|The MacDiarmid Institute for Advanced Materials and Nanotechnology, Wellington, New Zealand.|PolyBatics, Palmerston North, New Zealand.
Bernd H A
BH
Rehm
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001419:Bacteria / Q000235:genetics* / Q000276:immunology*; D001424:Bacterial Infections / Q000276:immunology* / Q000517:prevention & control; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D057005:Bioengineering; D016207:Cytokines / Q000096:biosynthesis; D000939:Epitopes / Q000276:immunology; D005818:Genetic Engineering; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization; D051379:Mice; D009154:Mutation; D011550:Pseudomonas aeruginosa / Q000276:immunology; D057188:Workflow
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D016207:Cytokines; D000939:Epitopes