Polio endgame options: will we have the vaccines needed?
Authors: Kimberly M Thompson
Journal: The Lancet (2019)

The Global Polio Eradication Initiative (GPEI), which launched in 1988 with a mandate to eradicate polio by 2000,1World Health AssemblyGlobal eradication of poliomyelitis by the year 2000 (resolution 41.28).http://www.who.int/csr/ihr/polioresolution4128en.pdfDate: 1988Date accessed: May 29, 2019Google Scholar has maintained its mission to stop and prevent the transmission of all three serotypes (1, 2, and 3) of wild poliovirus (WPV). Ultimately, ending all cases of poliomyelitis requires successful cessation of the use of all live-attenuated oral poliovirus vaccines (OPV) after certification of WPV eradication. Global transmission of serotype-2 WPV ended before 2000; in September, 2015, the world certified serotype-2 WPV eradication;2WHOGlobal eradication of wild poliovirus type 2 declared.http://polioeradication.org/news-post/global-eradication-of-wild-poliovirus-type-2-declared/Date: Sept 20, 2015Date accessed: November 28, 2016Google Scholar and in late April and early May, 2016, the GPEI globally coordinated the cessation of all use of serotype -2-containing OPV (OPV2), except for in emergency uses to respond to serotype-2 outbreaks.3WHOThe global switch: as it happens.http://polioeradication.org/news-post/the-global-switch-as-it-happens/Date: April 22, 2016Date accessed: November 28, 2016Google Scholar Global polio surveillance4WHOThree years with no wild poliovirus type 3.http://polioeradication.org/news-post/three-years-with-no-wild-poliovirus-type-3/Date: Nov 10, 2015Date accessed: November 28, 2016Google Scholar last reported a paralytic case caused by serotype-3 WPV in northern Nigeria in November, 2012, but, without official global certification of serotype-3 WPV eradication, the use of OPV containing serotype-3 polioviruses continues. Unfortunately, transmission of serotype-1 WPV in Pakistan and Afghanistan has led to a disturbing increase in reported paralytic cases: the GPEI reported 22 cases in 2017, 33 cases in 2018, and 24 cases in 2019, as of May 22.5WHOPolio this week as of 22 May 2019.http://polioeradication.org/polio-today/polio-now/this-week/Date: 2019Date accessed: May 22, 2019Google Scholar However, global cessation of OPV2 use did not proceed as intended everywhere.6Duintjer Tebbens RJ Thompson KM Polio endgame risks and the possibility of restarting the use of oral poliovirus vaccine.Expert Rev Vaccines. 2018; 17: 739-751Crossref PubMed Scopus (28) Google Scholar Outbreaks of serotype-2 circulating vaccine-derived polioviruses led to ten reported paralytic cases in 2019 (as of May 22), following the 71 reported cases in 2018, which exceeded the 33 cases caused by serotype-1 WPV in 2018.5WHOPolio this week as of 22 May 2019.http://polioeradication.org/polio-today/polio-now/this-week/Date: 2019Date accessed: May 22, 2019Google Scholar A response to serotype-2 circulating vaccine-derived poliovirus outbreaks requires the use of serotype-2 monovalent OPV. The more time that passes since mid-2016 without successfully stopping all serotype-2 live poliovirus transmission, the higher the risks become of needing to globally restart OPV2 production.6Duintjer Tebbens RJ Thompson KM Polio endgame risks and the possibility of restarting the use of oral poliovirus vaccine.Expert Rev Vaccines. 2018; 17: 739-751Crossref PubMed Scopus (28) Google Scholar The potential future need for OPV2 motivates the development of new and better strains that could offer greater benefits, lower risks, or both. A 2016 modelling analysis7Duintjer Tebbens RJ Thompson KM The potential benefits of a new poliovirus vaccine for long-term poliovirus risk management.Future Microbiol. 2016; 11: 1549-1561Crossref PubMed Scopus (15) Google Scholar suggested substantial potential health and financial benefits of ideal poliovirus vaccine strains for outbreak response. In The Lancet, Pierre Van Damme and colleagues8Van Damme P De Coster I Bandyopadhyay AS et al.A blinded phase 1 study of the safety and immunogenicity of two novel live attenuated monovalent (serotype 2) oral poliovirus vaccines in healthy adults.Lancet. 2019; (published online June 4.)http://dx.doi.org/10.1016/S0140-6736(19)31279-6Summary Full Text Full Text PDF PubMed Scopus (83) Google Scholar report the results of a phase 1 clinical trial of two novel OPV2 strains that were derived from a modified Sabin serotype-2 infectious cDNA clone and propagated in Vero cells to improve their genetic stability (S2/cre5/S15domV/rec1/hifi3 and S2/S15domV/CpG40). Their findings demonstrate the safety and immunogenicity of both strains in the 30 participants in the predominantly male (25 [83%] participants) study group of healthy adults (aged 21–50 years; mean, 32·3 years [SD 9·4]). All study participants met the inclusion criterion of previous immunisation with inactivated poliovirus vaccine. In their study, the first 15 sequentially enrolled adults received a single dose of one randomly selected novel OPV2 strain (which they were masked to), and they were then observed for 28 days in a highly-contained environment, and the second strain was later administered under the same test conditions. The results show some differences, with all 15 individuals who were given one strain (S2/cre5/S15domV/rec1/hifi3) excreting detectable virus (including seven participants for more than 28 days and one participant for 89 days), whereas 13 (87%) participants receiving the other strain (S2/S15domV/CpG40) shed the virus (including four participants for more than 28 days and one participant for 48 days). Observation of paralysis in transgenic mice suggested a lower risk of paralysis with both novel strains than with Sabin OPV2, using results from a previous study; however, the findings warrant further investigation in larger trials. These new findings represent an exciting first step toward the creation of a better OPV2 option in a world that might need it. Although the GPEI commissioned a relatively large stockpile of monovalent OPV2 for emergency outbreak responses after OPV2 cessation,9Duintjer Tebbens RJ Thompson KM Poliovirus vaccination during the endgame: insights from integrated modeling.Expert Rev Vaccines. 2017; 16: 577-586Crossref PubMed Scopus (24) Google Scholar ongoing use of monovalent OPV2 combined with a decreasing global immunity of the population to serotype-2 transmission (and increasing vulnerability to re-established transmission following importation of a serotype-2 circulating vaccine-derived poliovirus or OPV2-related virus)10Duintjer Tebbens RJ Hampton LM Thompson KM Implementation of coordinated global serotype 2 oral poliovirus vaccine cessation: risks of inadvertent trivalent oral poliovirus vaccine use.BMC Infect Dis. 2016; 16: 237Crossref PubMed Scopus (32) Google Scholar could, unfortunately, motivate a call to restart large-scale OPV2 production. Notably, even at high coverage, inactivated poliovirus vaccine cannot stop live poliovirus transmission in most places, as demonstrated by serotype-1 WPV transmission in Israel in 2013, which means that evidence of serotype-2 live poliovirus transmission could necessitate future OPV2 use.6Duintjer Tebbens RJ Thompson KM Polio endgame risks and the possibility of restarting the use of oral poliovirus vaccine.Expert Rev Vaccines. 2018; 17: 739-751Crossref PubMed Scopus (28) Google Scholar In the best-case scenario, the GPEI could aggressively stop all serotype-2 live poliovirus transmission quickly, and the world would never need to use any OPV2 in the future, which will make the new poliovirus vaccine strains unexercised insurance options. However, under other scenarios, world health leaders might need to make decisions about producing more OPV2, and this outcome could occur sooner rather than later. Questions will arise about the risks and benefits of the new strains relative to each other and to Sabin OPV2. Additionally, the relatively small, but non-zero risks associated with any OPV (ie, vaccine-associated paralytic polio and vaccine-derived polioviruses11Duintjer Tebbens RJ Pallansch MA Kew OM et al.Risks of paralytic disease due to wild or vaccine-derived poliovirus after eradication.Risk Analysis. 2006; 26: 1471-1505Crossref PubMed Scopus (132) Google Scholar, 12Duintjer Tebbens RJ Pallansch MA Wassalik SGF Cochi SL Thompson KM An economic analysis of poliovirus risk management policy options for 2013–2052.BMC Infect Dis. 2015; 15: 389Crossref PubMed Scopus (54) Google Scholar) become observable only with their use in large populations. If decisions to make more OPV2 must occur before completion of the clinical trials for the new OPV2 strains, fewer options will be available, which should motivate accelerated efforts to develop at least one new OPV2 strain as quickly as possible.8Van Damme P De Coster I Bandyopadhyay AS et al.A blinded phase 1 study of the safety and immunogenicity of two novel live attenuated monovalent (serotype 2) oral poliovirus vaccines in healthy adults.Lancet. 2019; (published online June 4.)http://dx.doi.org/10.1016/S0140-6736(19)31279-6Summary Full Text Full Text PDF PubMed Scopus (83) Google Scholar The question remains: can the GPEI stop serotype-2 transmission soon, or will the world need more OPV2, and will we have the best possible vaccines available when needed? I declare no competing interests. The safety and immunogenicity of two novel live attenuated monovalent (serotype 2) oral poliovirus vaccines in healthy adults: a double-blind, single-centre phase 1 studyWe found that the novel OPV2 candidates were safe and immunogenic in IPV-immunised adults, and our data support the further development of these vaccines to potentially be used for maintaining global eradication of neurovirulent type-2 polioviruses. Full-Text PDF Open Access