Oral vaccines have played huge part in the global battle to wipe out polio. When the WHO endorsed the goal of eradicating polio in 1988, some 350,000 children in 125 countries were being paralysed by the virus that caused the disease. That number has dropped precipitously and there were only about 1,000 cases of polio across the world last year.
If all goes well, this could be the year when the chain of transmission of wild polio is at last broken in India, one of just four countries in the world where the disease is still endemic.
The oral polio vaccines, which use live but weakened strains of the virus, are easy to administer as drops. But the live viruses they contain can occasionally turn virulent again. Such revertant viruses have the disease-causing potential of the wild forms and can readily spread.
Circulating vaccine-derived polio viruses have been implicated in over 15 outbreaks since 2000. One such outbreak began in Nigeria in 2005 and has still not been stamped out there. The virus turned up in two neighbouring countries as well and has been responsible for over 300 cases of paralysis.
In India, four lineages of vaccine-derived viruses that emerged independently have affected 16 patients in U.P. between July 2009 and March this year. So far this year there have been five such incidents and only one caused by a wild virus.
Using the oral vaccine could be considered an example of fighting fire with fire, remarked Neal Nathanson of the University of Pennsylvania's School of Medicine in an editorial commentary in the Journal of Infectious Diseases earlier this year.
“In countries or continents where wild polio viruses have been eliminated, there should be a transition from OPV to inactivated polio virus vaccine.” Many industrialised countries had already made this shift, he pointed out.
The inactivated vaccine (or IPV) is currently made from virulent strains of the virus that are grown in cell culture and then killed before being administered as an injection.
Ironically, the issue of which sort of vaccine to use is one that goes back to an epic squabble between two giants in the field, Jonas Salk and Albert Sabin. The former developed the inactivated vaccine while the latter was responsible for OPV.
America began immunising children against polio with the inactivated vaccine, which was the first to become available in the mid-1950s. It then moved to the Sabin vaccine based on live attenuated viruses in the early 1960s. However, with the steady trickle of polio cases from vaccine-derived viruses, the country switched back to the Salk vaccine in 2000.
But developing countries that want to make a similar switch face a major hurdle. The injectable vaccine is considerably more expensive than OPV. As a way out of this conundrum, one option that is being seriously looked at would involve a mix of the Salk and Sabin approaches — inactivated vaccines made from attenuated strains.
The WHO has been working with the National Institute for Public Health and the Environment (RIVM) in the Netherlands on the development of a safe, effective and affordable IPV using the Sabin virus strains and transferring the technology to vaccine manufacturers in developing countries.
In May this year, the global health agency announced that Pancea Biotech in India and LG Life Sciences in South Korea were the first two vaccine makers that had been selected to receive the RIVM's Sabin-IPV technology. Last month, the WHO again called for ‘Expressions of Interest' from other manufacturers in developing countries that wanted the technology.
Safer ways to produce the inactivated polio vaccine will be needed in a world where polio has been eradicated, noted the RIVM scientists in a recent paper in the journal Expert Review of Vaccines. “Development of an IPV based on [a] nonvirulent strain, such as the attenuated Sabin strains, will help to increase the biosafety of the manufacturing process. Employees will not be exposed to the wild-type polio strains and accidental spills will not cause an immediate danger of reintroduction of wild virulent polio strains into the world.”
The higher cost of IPV was the result of several factors, the scientists noted in another recent paper in the journal Vaccine. The IPV needed more vaccine per dose than the oral vaccine to elicit a protective immune response. Additional processing, including concentration, purification and inactivation of the virus, was necessary. Besides, quality control as well as the containment required in dealing with wild viruses also added to the vaccine's cost.
At present, the RIVM process to make Sabin-virus-based IPV was similar to the regular IPV production. “At this moment, the initial yields for Sabin-IPV are somewhat lower when compared to that for regular IPV,” noted Wilfried Bakker, senior scientist for viral vaccines and project manager at the RIVM, in an email.
However, they were already engaged in an optimisation process to raise yields to levels comparable to or better than the conventional IPV, he added. If the attenuated Sabin strains were used for IPV production, the same stringent and expensive biosafety conditions for handling the wild viruses would not be necessary, said Oliver Rosenbauer, a spokesperson for the WHO-led Global Polio Eradication Initiative. That would help bring down the cost of the vaccine quite significantly. In addition, more manufacturers making the vaccine in developing countries could stabilise the market as well.
Apart from the RIVM, the Japanese Polio Research Institute in Tokyo and the Chinese Academy of Medical Sciences' Kunming Institute of Medical Biology have also been working on IPVs using attenuated Sabin strains. Indeed, the Kunming Institute has already completed Phase-II clinical studies. (Scientists in the Netherlands expect to begin the Phase-I clinical trials of their vaccine in Europe shortly.)
Before Sabin-IPV vaccines can be cleared for general use, their safety and efficacy will, however, have to be proven through such clinical trials.