One billion doses and WHO prequalification of nOPV2: Implications for the global polio situation and beyond

With the COVID-19 pandemic abating, the only remaining Public Health Emergency of International Concern is polio 1.Remarkable progress has been made in reducing the global burden of poliomyelitis since the establishment of the Global Polio Eradication Initiative (GPEI) in 1988.However, achieving and sustaining eradication of all forms of polioviruses is being compromised by two sources of paralytic poliomyelitis: persisting pockets of type 1 wild poliovirus transmission in Afghanistan and Pakistan which reported 6 cases each in 2023 2 and ongoing outbreaks of circulating vaccine-derived polioviruses (cVDPV) 3.The latter, particularly those arising from type 2 Sabin oral polio vaccine (OPV) strains, have outnumbered cases of wild-type polio over the last few years, mostly due to outbreaks in the WHO African Region which affected 28 different countries in 2023 4.Sabin OPVs, in monovalent (mOPV) or trivalent (tOPV) forms, induce robust humoral and intestinal immunity, but while passing through the vaccinee's intestine can lose their attenuations and in rare cases can revert to neurovirulence.In settings of persistently poor immunity and low levels of sanitation and hygiene, such reverted OPV strains can establish person-to-person circulation and cause paralytic outbreaks 5.This risk is more prominent with type 2 poliovirus given there is limited mucosal immunity against this serotype of polio in young children following the 2016 global switch from tOPV (types 1, 2 and 3) to bivalent (types 1 and 3) OPV in essential immunization schedules 6,7.To mitigate the risk of cVDPV and vaccine-associated paralytic poliomyelitis (VAPP) and retain the advantages of OPV-ease of administration, affordability and favorable impact on interrupting virus transmission-a scientific consortium was established in 2011 to develop a novel oral polio vaccine type 2 (nOPV2).Designed at the molecular level to be more genetically stable than Sabin monovalent OPV type 2 (mOPV2) and to have a lower risk of reverting to neurovirulent variants 8, nOPV2 promises to break the vicious cycle of creating new cVDPV emergences while responding to cVDPV2 outbreaks 9.As illustrated in Fig 1, increasing numbers of cVDPV2 outbreaks derived from Sabin type 2 vaccines were detected following the tOPV to bOPV switch, peaking in 2019-20 before a gradual decline.To interrupt these outbreaks, there was widespread use of mOPV2 and to a lesser extent tOPV in mass vaccination campaigns between 2016 to 2021.In certain settings this led to seeding of new cVDPV2 emergences derived from Sabin OPV type 2 due to declining population immunity against type 2 poliovirus and insufficient coverage and delays in outbreak response.Given the risk of global spread of cVDPV2 outbreaks, and based on clinical data on the safety, immunogenicity, and genetic stability of nOPV2 generated in a series of clinical