PHILADELPHIA, PRNewswire-USNewswire/ -- While current vaccines have nearly eliminated polio worldwide, outbreaks have persisted in developing nations due in part to the vaccines' limitations. New research from Penn Dental Medicine offers proof for an alternative virus and cold-chain-free vaccine.
In collaboration with the CDC and FDA, the Penn Dental team developed an oral vaccine booster by manipulating plants to express a protein found in different polioviruses. The work, appearing in Plant Biotechnology Journal, was conducted by Henry Daniell, Professor of Biochemistry at Penn Dental Medicine and his research team.
Since the 1988 launch of the Global Polio Eradication Initiative, the incidence of disease has been greatly reduced. Yet challenges remain to ensure a polio-free world. Two vaccines -- bivalent oral poliovirus vaccine (bOPV) and the inactivated poliovirus vaccine (IPV) -- are currently used. IPV is safe, but is substantially more expensive than bOPV, and, as a shot, more difficult to administer than the bOPV oral drops. Also, it does not induce intestinal immunity, so vaccinated individuals can still shed the virus. A silent polio outbreak was reported in Israel recently after the use of IPV.
bOPV induces superior intestinal immunity compared with IPV and, thus, has the potential to better prevent transmission of polioviruses. However, due to the live attenuated virus in the oral polio vaccine, the virus can mutate and revert into a form of the virus that can cause paralysis. This risk led to the global withdrawal of tOPV, the trivalent OPV that targets all three serotypes of the virus, in April 2016. Eventually, all forms of the oral polio vaccine will be withdrawn globally. However, the importance of maintaining intestinal immunity against poliovirus remains a major concern.
To address the current vaccines' shortcomings, Daniell's group developed a booster vaccine that was free of any virus but would induce mucosal immunity to all three polio serotypes. In addition, their vaccine would be stable without refrigeration, making storage, transport, and administration easier.
Daniell's plant-based drug-development platform was suited to the task. Using it, his group modified the chloroplast genome to produce a universal polio virus protein. Because the gene for this protein is permanently inserted into the plant genome, plants can then be grown, freeze dried, and encapsulated for oral administration.
To induce immunity against polio, the researchers targeted a protein present in all three serotypes of polio. They fused it to a carrier protein, enabling it to cross mucosal surfaces, then confirmed they could stably express the fused protein in tobacco and lettuce plants.
Next they fed the freeze-dried plant material expressing the fused protein to mice to see if it could induce an immune response in mice that had been given an IPV vaccination.
"When the CDC performed tests on several hundred samples of sera from immunized mice, they found it could neutralize all three serotypes of poliovirus," says Daniell.
The researchers hope to pursue FDA approval for clinical studies in humans. The work was supported by the Bill & Melinda Gates Foundation and NIH.
