Food contaminating bacterial toxins could be neutralized with gene therapy.

gene therapyToxins produced by bacteria represent a considerable public health problem causing a considerable amount of food recalls per year and possible illness resulting in hospitalization.

A new study, by the Department of Infectious Disease and Global Health, has demonstrated a possible new way of neutralizing these toxins. The findings of the National Institutes of Health funded study appear in the August 29 issue of PLOS ONE.

Gene therapy represents a novel way to treat disease such as botulism, a rare but serious paralytic illness caused by a nerve toxin that is produced by the bacterium Clostridium botulinum. The same treatment is effective to combat bactria such as E-Coli food poisoning and C. difficile infection all produced by a microbial infection.

The researchers determined that a protein of the camelid family produces an unusual type of antibody that is particularly useful in developing effective, inexpensive antitoxin agents. A small piece of the camelid antibody — called a VHH — can bind to and neutralize the botulism toxin. It was determined that linking two or more different toxin-neutralizing VHHs results in VHH-based neutralizing agents (VNAs) that have extraordinary antitoxin potency and can be produced as a single molecule in bacteria at low cost.

A mice model was used to test treatment with gene therapy and the study findings determined that a single gene therapy led to prolonged production of VNA in blood and protected the mice from subsequent exposures to C. botulinum toxin for up to several months. All mice pretreated with VNA gene therapy survived when exposed to a normally lethal dose of botulinum toxin administered up to nine weeks later. Approximately 40 percent survived when exposed to this toxin as late as 13 or 17 weeks post-treatment. With gene therapy the VNA genetic material is delivered to animals by a vector that induces the animals to produce their own antitoxin VNA proteins over a prolonged period of time, thus preventing illness from toxin exposures.

“We envision this treatment approach having a broad range of applications such as protecting military personnel from biothreat agents or protecting the public from other toxin-mediated diseases such as C. difficile and Shiga toxin-producing E. coli infections,” said Shoemaker, the paper’s senior author. “More research is being conducted with VNA gene therapy and it’s hard to deny the potential of this rapid-acting and long-lasting therapy in treating these and several other important illnesses.”


Jean Mukherjee, Igor Dmitriev, Michelle Debatis, Jacqueline M. Tremblay, Gillian Beamer, Elena A. Kashentseva, David T. Curiel, Charles B. Shoemaker. Prolonged Prophylactic Protection from Botulism with a Single Adenovirus Treatment Promoting Serum Expression of a VHH-Based Antitoxin Protein. PLoS ONE, 2014; 9 (8): e106422 DOI: 10.1371/journal.pone.0106422

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