Continued use of poliovirus after eradication: hyper‐attenuated strains as a safe alternative for release testing of human immunoglobulins

Abstract

BACKGROUND Wild‐type poliovirus may be eradicated soon and under WHO GAPIII guidance, laboratory use will be discontinued or subject to strict containment. Per US Code of Federal Regulations, however, immunoglobulin lot release testing will still require use of replicating poliovirus. The suitability of S19 hyper‐attenuated and apathogenic poliovirus strains as alternatives to the currently used wild‐type virus in such a release assay was investigated. STUDY DESIGN AND METHODS S19 poliovirus strains were propagated in a commercial setting using good virological practices and maintenance of the S19 hyper‐attenuated genotype was confirmed by massively parallel sequencing. RESULTS The attenuated phenotype of the produced S19 stocks was confirmed in a highly sensitive mouse‐model. Equivalency in performance was seen in the lot release assay for the S19 and wild‐type polioviruses. CONCLUSION The deployment of such hyper‐attenuated and thoroughly characterized S19 stocks in these and other essential activities might reconcile final containment measures with continued safe use of poliovirus.

Commonly setting biological standards in rare diseases

“…We developed a novel high-resolution identity test for IPV products based on NGS [54] and we have recently led a collaborative study to establish the first International Standard for Sabin-IPV which provides a major contribution to these efforts [55]. Furthermore, hyper-attenuated S19 poliovirus strains unable to replicate in humans have been developed at NIBSC [56] and will be used as seeds for IPV production [57] as well as reagents for essential assays requiring the use of live poliovirus that will now be possible to carry out at lower containment levels, such as neutralization assays for seroprevalence studies or characterization of immunoglobulin preparations for medical use [58]. In addition, NIBSC in collaboration with the Universities of Leeds and Oxford and the John Innes Center (JIC) in the UK has made considerable progress in the research and development of non-infectious vaccine-like particles to be used as vaccines in the post-eradication era [53,59].…”

Assuring immune globulin potency in a world of changing pathogen challenges

“…Use of a hyperattenuated poliovirus strain that is incapable of causing paralytic disease can provide a pathway that would permit testing without Global Action Plan requirements. Promising advances in development and testing of hyperattenuated S19 poliovirus strains were described at the workshop . Such strains would need to be 1) noninfectious in people; 2) incapable of causing paralytic disease; 3) genetically stable and unable to regain paralytic potential; 4) easily cultured on conventional cells to high titers usable in neutralization assays; and 5) antigenically comparable to polioviruses currently used in neutralization assays.…”

“…Such strains would need to be 1) noninfectious in people; 2) incapable of causing paralytic disease; 3) genetically stable and unable to regain paralytic potential; 4) easily cultured on conventional cells to high titers usable in neutralization assays; and 5) antigenically comparable to polioviruses currently used in neutralization assays. The S19 strain described at the workshop is modified to eliminate gut infectivity and does not cause paralysis in susceptible mice when introduced into the spinal cord or in primates given high oral doses of virus . Based on this work, the S19 poliovirus strain described by Farcet et al was approved in June 2018, for use under Biosafety Level 2 conditions by the World Health Organization Containment Advisory Group, thus providing an attractive option for continued testing of IGs for poliovirus antibodies in IG products .…”

“…Promising advances in development and testing of hyperattenuated S19 poliovirus strains were described at the workshop. 17 Such strains would need to be 1) noninfectious in people; 2) incapable of causing paralytic disease; 3) genetically stable and unable to regain paralytic potential; 4) easily cultured on conventional cells to high titers usable in neutralization assays; and 5) antigenically comparable to polioviruses currently used in neutralization assays. The S19 strain described at the workshop is modified to eliminate gut infectivity and does not cause paralysis in susceptible mice when introduced into the spinal cord or in primates given high oral doses of virus.…”

“…The S19 strain described at the workshop is modified to eliminate gut infectivity and does not cause paralysis in susceptible mice when introduced into the spinal cord or in primates given high oral doses of virus . Based on this work, the S19 poliovirus strain described by Farcet et al was approved in June 2018, for use under Biosafety Level 2 conditions by the World Health Organization Containment Advisory Group, thus providing an attractive option for continued testing of IGs for poliovirus antibodies in IG products . Other, less well developed options include pseudotype virus neutralization assays or competitive enzyme‐linked immunosorbent assay (ELISA).…”