Evaluation and validation of next-generation sequencing to support lot release for a novel type 2 oral poliovirus vaccine
A novel, genetically-stabilized type 2 oral polio vaccine (nOPV2), developed to assist in the global polio eradication program, was recently the first-ever vaccine granted Emergency Use Listing by the WHO. Lot release tests for this vaccine included—for the first time to our knowledge—the assessment...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-08-01
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| Series: | Vaccine: X |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S259013622100019X |
| _version_ | 1818356752186343424 |
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| author | John O. Konz Tim Schofield Sarah Carlyle Rahnuma Wahid Azeem Ansari Jeroen R.P.M. Strating Ming Te Yeh Hasmik Manukyan Saskia L. Smits Erman Tritama Latri Rahmah Dori Ugiyadi Raul Andino Majid Laassri Konstantin Chumakov Andrew Macadam |
| author_facet | John O. Konz Tim Schofield Sarah Carlyle Rahnuma Wahid Azeem Ansari Jeroen R.P.M. Strating Ming Te Yeh Hasmik Manukyan Saskia L. Smits Erman Tritama Latri Rahmah Dori Ugiyadi Raul Andino Majid Laassri Konstantin Chumakov Andrew Macadam |
| author_sort | John O. Konz |
| collection | DOAJ |
| description | A novel, genetically-stabilized type 2 oral polio vaccine (nOPV2), developed to assist in the global polio eradication program, was recently the first-ever vaccine granted Emergency Use Listing by the WHO. Lot release tests for this vaccine included—for the first time to our knowledge—the assessment of genetic heterogeneity using next-generation sequencing (NGS). NGS ensures that the genetically-modified regions of the vaccine virus genome remain as designed and that levels of polymorphisms which may impact safety or efficacy are controlled during routine production. The variants present in nOPV2 lots were first assessed for temperature sensitivity and neurovirulence using molecular clones to inform which polymorphisms warranted formal evaluation during lot release. The novel use of NGS as a lot release test required formal validation of the method. Analysis of an nOPV2 lot spiked with the parental Sabin-2 strain enabled performance characteristics of the method to be assessed simultaneously at over 40 positions in the genome. These characteristics included repeatability and intermediate precision of polymorphism measurement, linearity of both spike-induced and nOPV2 lot-specific polymorphisms, and the limit-of-detection of spike-induced polymorphisms. The performance characteristics of the method met pre-defined criteria for 34 spike-induced polymorphic sites and 8 polymorphisms associated with the nOPV2 preparation; these sites collectively spanned most of the viral genome. Finally, the co-location of variants of interest on genomes was evaluated, with implications for the interpretation of NGS discussed. |
| first_indexed | 2024-12-13T20:02:12Z |
| format | Article |
| id | doaj.art-7805eacc4a144c3289cf7f764ff52931 |
| institution | Directory Open Access Journal |
| issn | 2590-1362 |
| language | English |
| last_indexed | 2024-12-13T20:02:12Z |
| publishDate | 2021-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Vaccine: X |
| spelling | doaj.art-7805eacc4a144c3289cf7f764ff529312022-12-21T23:33:08ZengElsevierVaccine: X2590-13622021-08-018100102Evaluation and validation of next-generation sequencing to support lot release for a novel type 2 oral poliovirus vaccineJohn O. Konz0Tim Schofield1Sarah Carlyle2Rahnuma Wahid3Azeem Ansari4Jeroen R.P.M. Strating5Ming Te Yeh6Hasmik Manukyan7Saskia L. Smits8Erman Tritama9Latri Rahmah10Dori Ugiyadi11Raul Andino12Majid Laassri13Konstantin Chumakov14Andrew Macadam15Center for Vaccine Innovation and Access, PATH, Seattle, WA, United States; Corresponding author at: Center for Vaccine Innovation and Access, PATH, Seattle, WA, United States.CMC Sciences, LLC, Germantown, MD 20876, United StatesNational Institute for Biological Standards and Control (NIBSC), Hertfordshire, United KingdomCenter for Vaccine Innovation and Access, PATH, Seattle, WA, United StatesCenter for Vaccine Innovation and Access, PATH, Seattle, WA, United StatesViroclinics Biosciences B.V., Rotterdam, the NetherlandsUniversity of California San Francisco, San Francisco, United StatesCenter for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United StatesViroclinics Biosciences B.V., Rotterdam, the NetherlandsP.T. Bio Farma, Bandung, IndonesiaP.T. Bio Farma, Bandung, IndonesiaP.T. Bio Farma, Bandung, IndonesiaUniversity of California San Francisco, San Francisco, United StatesCenter for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United StatesCenter for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United StatesNational Institute for Biological Standards and Control (NIBSC), Hertfordshire, United KingdomA novel, genetically-stabilized type 2 oral polio vaccine (nOPV2), developed to assist in the global polio eradication program, was recently the first-ever vaccine granted Emergency Use Listing by the WHO. Lot release tests for this vaccine included—for the first time to our knowledge—the assessment of genetic heterogeneity using next-generation sequencing (NGS). NGS ensures that the genetically-modified regions of the vaccine virus genome remain as designed and that levels of polymorphisms which may impact safety or efficacy are controlled during routine production. The variants present in nOPV2 lots were first assessed for temperature sensitivity and neurovirulence using molecular clones to inform which polymorphisms warranted formal evaluation during lot release. The novel use of NGS as a lot release test required formal validation of the method. Analysis of an nOPV2 lot spiked with the parental Sabin-2 strain enabled performance characteristics of the method to be assessed simultaneously at over 40 positions in the genome. These characteristics included repeatability and intermediate precision of polymorphism measurement, linearity of both spike-induced and nOPV2 lot-specific polymorphisms, and the limit-of-detection of spike-induced polymorphisms. The performance characteristics of the method met pre-defined criteria for 34 spike-induced polymorphic sites and 8 polymorphisms associated with the nOPV2 preparation; these sites collectively spanned most of the viral genome. Finally, the co-location of variants of interest on genomes was evaluated, with implications for the interpretation of NGS discussed.http://www.sciencedirect.com/science/article/pii/S259013622100019XNext-generation sequencingValidationPoliovirusOPVNeurovirulence |
| spellingShingle | John O. Konz Tim Schofield Sarah Carlyle Rahnuma Wahid Azeem Ansari Jeroen R.P.M. Strating Ming Te Yeh Hasmik Manukyan Saskia L. Smits Erman Tritama Latri Rahmah Dori Ugiyadi Raul Andino Majid Laassri Konstantin Chumakov Andrew Macadam Evaluation and validation of next-generation sequencing to support lot release for a novel type 2 oral poliovirus vaccine Vaccine: X Next-generation sequencing Validation Poliovirus OPV Neurovirulence |
| title | Evaluation and validation of next-generation sequencing to support lot release for a novel type 2 oral poliovirus vaccine |
| title_full | Evaluation and validation of next-generation sequencing to support lot release for a novel type 2 oral poliovirus vaccine |
| title_fullStr | Evaluation and validation of next-generation sequencing to support lot release for a novel type 2 oral poliovirus vaccine |
| title_full_unstemmed | Evaluation and validation of next-generation sequencing to support lot release for a novel type 2 oral poliovirus vaccine |
| title_short | Evaluation and validation of next-generation sequencing to support lot release for a novel type 2 oral poliovirus vaccine |
| title_sort | evaluation and validation of next generation sequencing to support lot release for a novel type 2 oral poliovirus vaccine |
| topic | Next-generation sequencing Validation Poliovirus OPV Neurovirulence |
| url | http://www.sciencedirect.com/science/article/pii/S259013622100019X |
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