Shigella-Derived Vector for Vaccines to Induce a Protective Immune Response Against Dysentery

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Researchers
Anthony T. Maurelli
Managed By
Zahara M. Jaffer
Assistant Director 352-392-8929
Patent Protection
US Patent 9,434,772

Utilizes Recombinant Shigella Vectors to Develop Live, Attenuated Vaccine Strains to Protect Against Shigellosis, E. Coli, and More

These recombinant Shigella vectors provide an improved platform to develop a vaccine strain effective against Shigella or Escherichia Coli. Vaccines often use attenuated strains of bacteria to protect humans and animals from disease. Modified vaccine strains have a reduced ability to cause disease yet retain sufficient pathogenic potential to stimulate a protective immune response. Shigella is a Gram-negative bacteria that causes shigellosis, or bacillary dysentery, an intestinal disease that causes abdominal pain, diarrhea, and fever. No effective vaccine strain of Shigella to protect humans against bacillary dysentery exists because researchers are unable to balance the strain’s need to invade the intestinal epithelium with its need for reduced pathogenicity. Investigators seek to achieve this balance by mutating or deleting genes on the Shigella invasion plasmid. This strategy is unfavorable because it is time consuming, and the strains still may cause symptomatic reactions such as diarrhea and/or fever.

Researchers at the University of Florida have developed recombinant Shigella vectors that provide an improved platform for developing attenuated vaccine strains of Shigella. This platform, called the Shigella minimal invasion plasmid, successfully achieves the balance between immunogenicity and reduced reactogenicity and could be used in vaccines to prevent shigellosis, E. Coli bacterial infections, and other diseases.

Application

Recombinant Shigella vectors that improve the development of attenuated vaccine strains to protect against Shigella and other diseases

Advantages

  • Adds individual recognized virulence genes back to the Shigella minimal invasion plasmid, allowing one to determine the contribution of each gene to virulence and reactogenicity
  • Utilizes a recombinant Shigella vector, acting as a live vaccine platform for delivery or expression of recombinant antigens in host cells
  • Establishes a delivery platform to receive other genes in addition to Shigella, facilitating delivery of DNA vaccines to mucosal lymphoid tissues

Technology

Working from a “bottom up” strategy, UF researchers determined the minimal set of genes on a Shigella invasion plasmid that mediate invasion and multiplication in host epithelial cells. The genes were cloned into a plasmid and form a Shigella minimal invasion plasmid (SMIP). The SMIP, when transferred into a plasmid-cured strain of Shigella, forms a usable vaccine strain. Immunogenic protein encoding genes from a pathogen other than Shigella may be used to augment the immunogenicity of the SMIP as well. Thus, the plasmid-cured Shigella, with a SMIP, serves as a system for delivering any antigen of interest. Ultimately, this platform can induce an immune response in a subject, whether to Shigella or to another bacterial, viral, or parasitic protein of interest.