Molecular and Antigenic Characterization of a Highly Evolved Derivative of the Type 2 Oral Poliovaccine Strain Isolated from Sewage in Israel

Abstract

An unusual, highly diverged derivative of the Sabin type 2 oral poliovaccine (OPV) strain was recovered from environmental samples during routine screening for wild polioviruses. Virus was cultivated in L20B cells and then passaged on BGM cells at 40°C (RCT [reproductive capacity at supraoptimal temperature]-positive marker) to select against most OPV strains. All but 1 of 25 RCT-positive OPV-derived environmental isolates were antigenically and genetically (>99.5% VP1 sequence match) similar to the respective Sabin strains. However, isolate PV2/4568-1/ISR98 (referred to below as 4568-1) escaped neutralization with Sabin 2-specific monoclonal antibodies and cross-adsorbed sera, and had multiple nucleotide substitutions (220 of 2,646; 8.3%) in the P1 capsid region. Fourteen of the 44 associated amino acid substitutions in the capsid mapped to neutralizing antigenic sites. Neutralizing titers in the sera of 50 Israeli children 15 years old were significantly lower to 4568-1 (geometric mean titer [GMT], 47) than to Sabin 2 (GMT, 162) or to the prototype wild strain, PV2/MEF-1/EGY42 (GMT, 108). Two key attenuating sites had also reverted in 4568-1 (A 481 to G in the 5 untranslated region and the VP1 amino acid I 143 to T), and the isolate was highly neurovirulent for transgenic mice expressing the poliovirus receptor (PVR-Tg21 mice). The extensive genetic divergence of 4568-1 from the parental Sabin 2 strain suggested that the virus had replicated in one or more people for ϳ6 years. The presence in the environment of a highly evolved, neurovirulent OPV-derived poliovirus in the absence of polio cases has important implications for strategies for the cessation of immunization with OPV following global polio eradication.

Vaccine-Derived Polioviruses and the Endgame Strategy for Global Polio Eradication

“…These genetic properties correlate with high neurovirulence for transgenic mice expressing the CD155 receptor (12,84,113,117,119,169,177,180,223,226) and the capacity to replicate to high titers in cell culture at supraoptimal temperatures (12,84,117,226). Moreover, all VDPV isolates characterized so far have antigenic properties distinct from the original Sabin strains (12,71,84,117,177,180,226). The antigenic differences from the Sabin strains are less pronounced for type 2 cVDPVs than for type 1 cVDPVs, possibly because selection against the Sabin 2 antigenic sites is less intense during replication in immunocompetent per-sons (133).…”

Dynamics of Evolution of Poliovirus Neutralizing Antigenic Sites and Other Capsid Functional Domains during a Large and Prolonged Outbreak

“…X-ray crystallographic studies have shown that the greatest structural differences in the capsids across PV serotypes reside in the exposed loops that form the NAg sites (26)(27)(28)(29). Amino acid variability within PV serotypes is highest in the NAg sites and in the N terminus of VP1 (33)(34)(35)(36)(37).…”

Risks of Paralytic Disease Due to Wild or Vaccine‐Derived Poliovirus After Eradication

“…(70)(71)(72) Table III lists iVDPVs detected to date. (1,38,39,45,48,71,(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89) Our definition of an outbreak as at least one paralytic case suggests that we should count as an outbreak any iVDPV viruses that spread to the community and cause at least one para-lytic case. In this context, iVDPV excretors who developed paralytic poliomyelitis themselves do not represent outbreaks, given their original infection with Sabin-like viruses (i.e., not with a VDPV virus).…”