PLoS Pathogens
http://journals.plos.org/plospathogens/
(Accessed 2 January 2016)

.
New Strains Intended for the Production of Inactivated Polio Vaccine at Low-Containment After Eradication
Sarah Knowlson, John Burlison, Elaine Giles, Helen Fox, Andrew J. Macadam, Philip D. Minor
Research Article | published 31 Dec 2015 | PLOS Pathogens
10.1371/journal.ppat.1005316
Abstract
Poliomyelitis has nearly been eradicated through the efforts of the World Health Organization’s Global Eradication Initiative raising questions on containment of the virus after it has been eliminated in the wild. Most manufacture of inactivated polio vaccines currently requires the growth of large amounts of highly virulent poliovirus, and release from a production facility after eradication could be disastrous; WHO have therefore recommended the use of the attenuated Sabin strains for production as a safer option although it is recognised that they can revert to a transmissible paralytic form. We have exploited the understanding of the molecular virology of the Sabin vaccine strains to design viruses that are extremely genetically stable and hyperattenuated. The viruses are based on the type 3 Sabin vaccine strain and have been genetically modified in domain V of the 5’ non-coding region by changing base pairs to produce a cassette into which capsid regions of other serotypes have been introduced. The viruses give satisfactory yields of antigenically and immunogenically correct viruses in culture, are without measurable neurovirulence and fail to infect non-human primates under conditions where the Sabin strains will do so.
Author Summary
New polio vaccines will be needed to safeguard global eradication: Sabin strains are known to evolve to fill the niche left by wild-strains so their long-term use is incompatible with eradication; most current inactivated vaccine is made from wild polioviruses so that production presents a significant biosecurity risk. We have developed new strains for Inactivated Polio Vaccine (IPV) production with negligible risk to the human population should they escape. Sabin’s live-attenuated vaccines are variants of wild strains selected by the use of unnatural cell substrates, hosts and growth conditions. Unsurprisingly these variants evolve back towards wild-type properties during replication in, and transmission between, their natural hosts. An understanding of the molecular basis of these pathways led us to design novel vaccine strains that are very highly attenuated and arguably cannot replicate in people and whose opportunities for reversion during replication in cell culture are severely restricted. At the same time, the strains can feasibly be produced on a large-scale and they are as immunogenic as current IPV. These attributes allow for safe vaccine production in the post-eradication world.