Harnessing the power of cholera toxin to generate a vaccine against PRRS virus leads to a surprising

Large-scale cholera outbreaks, such as those that occurred after the 2010 earthquake in Haiti or even more recently after hurricane Matthew hit in 2016, claim a large number of victims. Vibrio cholerae the bacterial agent responsible for cholera infections attacks its victims with an arsenal of naturally produced weapons, including cholera toxin (CT). Powerful toxins already exist in nature, so why not re-engineer these naturally occurring toxins for therapeutic use?

This concept has been explored in many biomedical laboratories despite the large number of technical challenges that must be overcome before a toxin is considered safe for widespread therapeutic use. The proof in principle is the use of botulinum toxin, also of bacterial origin, to treat serious infections or sold as botox for cosmetic purposes.

This success inspired Dr. Denis Archambault’s group at UQAM in collaboration with Dr. Martin Lessard from Agriculture and Agri-food Canada to take up the challenge. They decided to develop a vaccine to stop porcine reproductive and respiratory syndrome virus (PRRSV) in its tracks. Stopping this virus would save the porcine industry from annual losses totalling 150 million dollars.

This is not Dr. Archambault’s first foray into vaccinology; he has already generated chimeric molecules called M-GP5 that are able to induce partial immunity against infections caused by PRRSV in pigs. This time around, the goal was to achieve full immunity against the virus. This ambitious goal led Dr. Archambault and his colleague Dr. Lessard from the Research and Development Center of Sherbrooke to re-engineer CT. The strategy was to use CT to stimulate both mucosal and humoral immune responses to prepare it to fight against PRRSV. After overcoming numerous technical challenges, these researchers successfully engineered CT to produce a new chimeric molecule called M-GP5-CTB. They were now ready to start testing their molecule in pigs. This experiment yielded unexpected results, while the addition of CT to the fusion molecule does induce an immune response in pigs; the M-GP5 is no longer recognized by the immune system.

These Swine and Poultry Infectious Diseases Research Centre (CRIPA) researchers must now go back to the drawing board and redesign their chimer. This will allow them to identify the right molecular architecture that will prepare the immune system to stop PRRSV infections. To be continued…

To read the whole story, please see: The Cholera Toxin B Subunit (CTB) Fused to the Porcine Arterivirus Matrix M and GP5 Envelope Proteins Fails to Enhance the GP5-Specific Antibody Response in Pigs Immunized with Adenovectors. Auteurs Roques E, Lessard M, Archambault D.

Source: Mol Biotechnol. 2015 Aug;57(8):701-8. https://link.springer.com/article/10.1007/s12033-015-9861-6/fulltext.html