AS the world is approaching the goal of polio virus eradication, there are concerns among scientists about post-eradication manufacturing and stockpiling of vaccine containing the live virus that could escape and repopulate the environment. A study published in a recent issue of PLOS Pathogens reports the generation of new vaccine strains that appear both effective and unable to cause disease after an accidental or intended release.
Different types of polio vaccines currently exist, but they are not entirely safe. Live attenuated (weakened) vaccine strains carry genetic mutations that prevent them from causing the disease, but in rare cases they can revert to a more virulent virus. There are also instances of live attenuated virus surviving in the gut of immune-compromised individuals and being shed into the environment through their faeces. Inactivated polio vaccines (IPVs) are themselves safe, but their production at present involves growing large amounts of the wild-type (active virulent) virus that is then killed with the chemical formalin.
After eradication, the World Health Organisation plans to stop the use of live attenuated polio vaccines. In addition, to improve safety, the WHO has strongly encouraged new manufacturers to switch the source of inactivated virus from virulent wild-type strains to the attenuated strain called the Sabin strain, named after the polio vaccine pioneer Albert Sabin. Arguing that the attenuated Sabin strain is unstable and therefore potentially problematic, Philip Minor, from the National Institute for Biological Standards and Control, U.K., and associates presented data on the attenuated strains they propose as a safer alternative source for IPVs.
The researchers started with a Sabin vaccine strain whose attenuation and reversion was well understood and modified a particular region of the viral RNA in ways they predicted would make the resulting strains genetically stable (i.e., they would not revert to wild-type or other virulent forms). They then compared these new strains with both the original Sabin vaccine strain and the wild-type strain currently used in the production of IPVs.
Besides testing the genetic stability of the new strains, the researchers examined their ability to grow in a tissue culture (necessary for vaccine production), their risk for causing paralysis in mice engineered to carry a human polio-virus receptor, and whether after inactivation they effectively immunised rats. In all these tests, the new strains behaved as predicted: effective, suitable to mass production, and safer than the alternatives. “We have developed new strains for IPV production with negligible risk to the human population should they escape,” the researchers conclude and add that the attributes of the new strains “allow for safe vaccine production in the post-eradication world”.