Neurovirulent Vaccine-Derived Polioviruses in Sewage from Highly Immune Populations

Abstract

BackgroundVaccine-derived polioviruses (VDPVs) have caused poliomyelitis outbreaks in communities with sub-optimal vaccination. Israeli environmental surveillance of sewage from populations with high (>95%) documented vaccine coverage of confirmed efficacy identified two separate evolutionary clusters of VDPVs: Group 1 (1998–2005, one system, population 1.6×106) and Group 2 (2006, 2 systems, populations 0.7×106 and 5×104).Principal FindingsMolecular analyses support evolution of nine Group 1 VDPVs along five different lineages, starting from a common ancestral type 2 vaccine-derived Sabin-2/Sabin-1 recombinant strain, and independent evolution of three Group 2 VDPVs along one lineage starting from a different recombinant strain. The primary evidence for two independent origins was based on comparison of unique recombination fingerprints, the number and distribution of identical substitutions, and evolutionary rates. Geometric mean titers of neutralizing antibodies against Group 1 VDPVs were significantly lower than against vaccine strains in all age-group cohorts tested. All individuals had neutralizing titers >1∶8 against these VDPVs except 7% of the 20–50 year cohort. Group 1 VDPVs were highly neurovirulent in a transgenic mouse model. Intermediate levels of protective immunity against Group 2 VDPVs correlated with fewer (5.0+1.0) amino acid substitutions in neutralizing antigenic sites than in Group 1 VDPV's (12.1±1.5).SignificanceVDPVs that revert from live oral attenuated vaccines and reacquire characteristics of wild-type polioviruses not only threaten populations with poor immune coverage, but are also a potential source for re-introduction of poliomyelitis into highly immune populations through older individuals with waning immunity. The presence of two independently evolved groups of VDPVs in Israel and the growing number of reports of environmental VDPV elsewhere make it imperative to determine the global frequency of environmental VDPV. Our study underscores the importance of the environmental surveillance and the need to reconsider the global strategies for polio eradication and the proposed cessation of vaccination.

Role of environmental poliovirus surveillance in global polio eradication and beyond

“…Frequent isolation by ENV of vastly drifted aVDPV strains genetically resembling iVDPV [47,[49][50][51] suggests that long-term PV excretion is not limited to immunedeficient individuals known to the health system, or if known to the health system not recognized as chronically excreting PV.…”

Intensified environmental surveillance supporting the response to wild poliovirus type 1 silent circulation in Israel, 2013

“…The methods used for sample concentration and virus purification from sewage samples during the routine surveillance period have been previously described in detail [11]. Poliovirus was plaque isolated in L20B cells (2 mL of sample inoculated into four 10 cm tissue culture plates) and the number of plaques isolated on each plate was recorded.…”

“…In addition, it has detected two lineages of highly diverged type 2 VDPV in the Tel Aviv sewage system, excreted by single individuals [9][10][11], demonstrating the high sensitivity of environmental surveillance for monitoring large populations. Laboratory methods for sample treatment and poliovirus isolation, including the plaque formation approach, are also a major factor in the sensitivity of the environmental surveillance, as reviewed by Hovi et al [3].…”

“…In December 2012, WPV1-SOAS was detected in sewage collected from Cairo, Egypt [11], where systematic environmental surveillance for poliovirus has been in place since 2000. A large immunisation campaign initiated as a response led to the disappearance of the virus from the sewage and, by implication, from the population at large [12].…”

Polio endgame risks and the possibility of restarting the use of oral poliovirus vaccine

“…The seeding of new iVDPVs stops at or near the time of OPV cessation, which means that the risks of reintroduction of live polioviruses into populations from iVDPV excretors should decrease with the time since OPV cessation. In the context of widespread use of OPV or populations with limited fecal-oral transmission that use IPV-only, any introduced live polioviruses, including iVDPVs, typically do not cause widespread transmission [35–37]. However, as population immunity to transmission declines following OPV cessation, any remaining iVPDVs excreted may begin to cause transmission in the surrounding communities [38].…”