Scientists from the National Institute for Biological Standards Control (NIBSC) have contributed to the development of a novel vaccine believed to be a potential gamechanger in the efforts to eradicate polio.
This work, carried out in collaboration with Raul Andino at the University of California and funded by the Bill and Melinda Gates Foundation, involved engineering a new version of the oral poliovirus vaccine (OPV) that may well be incapable of reverting into a disease-causing form.
The vaccine has been evaluated in pre-clinical and clinical studies and was found to be safe and effective. These latest findings have now been published in the journal Cell Host and Microbe.
Coloured transmission electron micrograph of poliovirus particles
Thanks to a well-coordinated global vaccination programme, polio is on the brink of eradication. The OPV, which contains live attenuated strains of poliovirus was originally developed by Albert Sabin in the 1950s and has been central to the success of this initiative. The vaccine stimulates high levels of immunity in the intestine that effectively interrupts person to person transmission, while its low cost and oral route of administration make it well suited to mass vaccination campaigns.
Despite its advantages, the current OPV has a significant drawback that may undermine the polio endgame strategy. It was discovered that in regions with low vaccine coverage, the OPV strains can circulate within a population and mutate to regain virulence leading to outbreaks of disease. In fact, the number of cases of circulating vaccine-derived poliovirus (cVDPV) now exceed those caused by wild poliovirus strains. Consequently, there is an urgent need for a novel, safer vaccine with greater genetic stability.
The scientists involved in this study were able to apply a rational approach to the design of the new vaccine based on their existing knowledge of the molecular basis of polio vaccine attenuation and the evolution of virulence.
They introduced a total of five modifications into the Sabin type 2 (Sabin 2) strain of the OPV which is responsible for the majority of cVDPV cases. When combined, these modifications act like a multi-layered safety net that makes the vaccine much less likely to acquire new mutations.
Earlier studies had revealed the existence of a single ‘gatekeeper’ mutation that often occurs shortly after OPV immunisation and makes the reversion to virulence possible. Therefore, the scientists modified this region of the viral genome in a way that ensures that the gate remains closed. They also introduced a design element that reduces the likelihood of this protective modification being lost if the strain exchanges genetic material with circulating enteroviruses.
Additionally, the scientists targeted the gene encoding the viral RNA polymerase enzyme and introduced modifications that reduce the number of errors made during replication and make genetic recombination less likely.Experiments carried out in cell culture and a mouse model confirmed that this new vaccine strain was more genetically stable than the Sabin 2 strain from which it was derived. Similarly, the results of a phase I clinical trial involving 15 healthy adults revealed that the new vaccine stimulated an immunogenic response and completely retained its genetic stability.
Dr Andrew Macadam, Principal Scientist at NIBSC and the lead author of this study comments that:“These data are very encouraging and suggest that the design features of this new strain are indeed effective. The risk of the strain evolving into a pathogenic virus should be dramatically reduced compared to the current vaccine.”
The results of this study indicate that this novel polio vaccine could play a key role in the polio eradication strategy going forward.
Results of phase II trials are being analysed to establish how the vaccine behaves in a larger population and the World Health Organisation is assessing whether this vaccine should be granted Emergency Use Listing that could see its introduction in outbreak regions as early as 2020. This would represent the first ever use in humans of a live-attenuated vaccine developed through rational design.
More information about our research into novel polio vaccines is available here.