March 30, 2014
Tobacco May One Day Be Used To Fight West Nile
Brett Smith for redOrbit.com - Your Universe Online
Tobacco is commonly associated with causing disease, but a new methodology developed by scientists at Arizona State University and several other institutions uses the plant to generate a potential therapy for treating West Nile virus – which currently has no cure.
According to a report published on Thursday in the open-access journal PLOS ONE, the team used tobacco to generate monoclonal antibodies (MAbs) and their derivatives, which have been demonstrated to neutralize and safeguard mice against the deadly challenge of West Nile virus.
"The overarching goal of our research is to create an innovative, yet sustainable and accessible, low cost solution to combat the global threat of West Nile virus," said team leader Qiang "Shawn" Chen, a researcher at Arizona State University's Biodesign Institute, in a recent statement.
MAbs are generally produced in animal hosts and have never been manufactured in a plant system until now. To produce the possible therapeutics, the group used young tobacco plants plus a protein manifestation system to create and harvest a protein essential for combating disease. The team said they were able to create MAbs in ten days.
"The goal of this latest research was twofold," said Chen. "First, we wanted to show proof-of-concept, demonstrating that tobacco plants can be used to manufacture large and complex MAb-based therapeutics. Secondly, we've wanted to improve the delivery of the therapeutic into the brain to combat West Nile virus at the place where it does the greatest harm."
Spread by mosquitoes, West Nile virus is a potentially lethal disease that targets the central nervous system. Previous research form the Arizona team showed that a MAb called pHu-E16 could neutralize West Nile infection and protect mice from exposure. However, the team was not able to build up sufficient levels of the antibody in the brain, which is shielded from the circulatory system via the blood-brain barrier.
In the new study, the team made six new variants that could target the brain and reduce the effects of West Nile virus. Next, they infected mice with a lethal amount of West Nile virus and escalating amounts of a MAb therapeutic were administered as a single dose within 24 hours of infection.
In a different experiment, Chen's team examined if the therapeutic MAb, called Tetra pHu-E16, might be effective after infection. For this experiment, the therapy was given 4 days after West Nile virus infection, when the virus has already propagated to the brain. In both cases, the MAbs protected up to 90 percent of the mice from fatal disease.
Chen said the result of this study gives promise to the development of a plant-based system to dramatically lower the costs of commercial manufacturing of MAbs.
"This study is a major step forward for plant-based MAbs, and also demonstrates for the first time the capacity of plants to express and assemble large, complex and functional tetravalent MAb complexes," he said.
"It is our hope that these results may usher in new age of cost-effective, MAbs therapeutics against WNV and other neurological diseases," Chen added. "Our next step is to move this forward with the development of bifunctional MAbs that can target to the brain with the ultimate goal of entering human clinical trials."