For decades, the world has relied on 2 vaccines to prevent and control poliomyelitis: inactivated polio vaccine (IPV), produced by using formalin to inactivate 3 naturally occurring (ie, wild-type) polioviruses; and live attenuated oral poliovirus vaccine (OPV), created by Albert Sabin by passage of wild-type polioviruses in cell culture and/or nonhuman primates. Global use of both vaccines, each in different settings, has brought the world close to the long-sought goal of polio eradication, which is in reach if security threats and barriers to access can be overcome in Afghanistan and Pakistan, the countries where wild type 1 polioviruses remain endemic .
But even with success in these difficult locations, there is a looming threat to eradication that must be met to ensure that the Earth is free of all poliovirus disease. OPV viruses are genetically unstable and lose attenuating mutations upon replication in the human GI tract while gaining fitness and acquiring the ability to spread in settings with low immunization rates and a high force of infection due to poor sanitation [2, 3]. Twenty years ago, a polio outbreak on the island of Hispaniola firmly established the potential for vaccine-derived polioviruses (VDPVs) to seed new polio outbreaks. Now, circulating VDPV cause more poliomyelitis cases than wild-type viruses [4, 5].
To mitigate the risks of VDPV emergences, the Global Polio Eradication Initiative (GPEI) introduced a strategy of phased withdrawal of the 3 Sabin strains from global use, beginning with the coordinated replacement of trivalent OPV with bivalent type 1/type 3 OPV in April–May 2016 and concurrent introduction of IPV. Since then, the continued circulation of type 2 VDPVs into 2019 at higher than expected rates in some African countries has become a major concern [1, 6]. Despite this formidable challenge, we remain optimistic that the GPEI will ultimately succeed, leading to cessation of all OPV use.
After OPV cessation, recurrent polio could theoretically emerge from unrecognized VDPV circulation, community spread from an immunodeficient long-term excreter of VDPV, or inadvertent release from a vaccine-production site or other sites. The World Health Organization takes the threat of “relapse” of poliovirus circulation very seriously and has adopted strict biosafety and biosecurity requirements for all facilities that possess or may potentially possess live polioviruses . However, no measures can guarantee that all virus stocks remain accounted for or that virus cannot emerge from other sources or even be synthesized from chemicals. Therefore, maintaining population immunity against polioviruses for the foreseeable future remains an important component of the polio eradication endgame. At this time, this will only be accomplished by continued worldwide use of IPV.
The need to produce enough IPV to immunize the >100 million children living in countries that previously relied on OPV alone for routine infant immunization, in addition to the high price of currently licensed conventional IPV, have created an opportunity for new IPV manufacturers to enter the global market, including those in developing countries. We anticipate that several new, more economical IPVs will become available over the next 5–7 years, some as a stand-alone IPV product and others combined in a hexavalent formulation with diphtheria toxoid, tetanus toxoid, whole-cell pertussis vaccine, hepatitis B vaccine, and Haemophilus influenzae type B antigens. Most new IPVs will be made with Sabin strain viruses, which increase biosafety and reduce the risks to the population from a breach of containment . The first Sabin strain IPV (sIPV) was developed in the United States in the 1980s but was not licensed for use . Improvements in manufacturing technology resulting in enhanced yields prior to inactivation have now made sIPV commercially feasible and further encouraged sIPV development. sIPV combined with tetanus and diphtheria toxoids and acellular pertussis vaccine was introduced in Japan in 2012, and 2 standalone sIPVs have recently been licensed for distribution in China .
Until now, there has been no accepted international standard to measure the potency of a candidate sIPV in vitro. The report by Martin et al in this issue of The Journal of Infectious Diseases describes the results of an international collaboration of sIPV manufacturers and reference laboratories to test the assay characteristics of 2 candidate sIPV standards against a panel of 3 sIPVs and 2 conventional IPV international standards in the enzyme immunoassay format. After rigorous evaluation, the sIPV standards proved superior to the conventional standards in reducing interlaboratory variability. Based on this work, 1 candidate, 17/160, was accepted by the World Health Organization Expert Committee on Biological Standardization as the first international standard for sIPV in November 2018.
The original intent of the collaboration was to assign potency units for the new sIPV international standard by cross-calibrating the new standard to the existing international standard for potency, which is based on IPV formulated from wild poliovirus strains. An unexpected result of the study was that not only was such calibration not scientifically feasible, but an entirely new potency unit different from the one used for conventional IPV had to be established for sIPVs. As a result, a new potency unit (the sD antigen unit) was adopted. The availability of the new sIPV international standard and the new sD antigen unit will facilitate and harmonize the development and regulation of current and future sIPVs that will be required to provide vaccine coverage in countries at risk of emergent VDPV outbreaks, before and after the use of all OPVs are discontinued, and to secure a future free of poliomyelitis from any source.
Potential conflicts of interest. J. F. M. reports that his employer, the Bill and Melinda Gates Foundation, partially funded the collaborative study described here. K. C. certifies no potential conflicts of interest. The authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.