Assessment of genetic changes and neurovirulence of shed Sabin and novel type 2 oral polio vaccine viruses

Abstract Sabin-strain oral polio vaccines (OPV) can, in rare instances, cause disease in recipients and susceptible contacts or evolve to become circulating vaccine-derived strains with the potential to cause outbreaks. Two novel type 2 OPV (nOPV2) candidates were designed to stabilize the genome ag...

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Autores principales:	Rahnuma Wahid, Laina Mercer, Andrew Macadam, Sarah Carlyle, Laura Stephens, Javier Martin, Konstantin Chumakov, Majid Laassri, Svetlana Petrovskaya, Saskia L. Smits, Koert J. Stittelaar, Chris Gast, William C. Weldon, Jennifer L. Konopka-Anstadt, M. Steven Oberste, Pierre Van Damme, Ilse De Coster, Ricardo Rüttimann, Ananda Bandyopadhyay, John Konz
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/9baa83fb25b24bc98ad916e2a20f707d
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spelling	oai:doaj.org-article:9baa83fb25b24bc98ad916e2a20f707d2021-12-02T16:24:51ZAssessment of genetic changes and neurovirulence of shed Sabin and novel type 2 oral polio vaccine viruses10.1038/s41541-021-00355-y2059-0105https://doaj.org/article/9baa83fb25b24bc98ad916e2a20f707d2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00355-yhttps://doaj.org/toc/2059-0105Abstract Sabin-strain oral polio vaccines (OPV) can, in rare instances, cause disease in recipients and susceptible contacts or evolve to become circulating vaccine-derived strains with the potential to cause outbreaks. Two novel type 2 OPV (nOPV2) candidates were designed to stabilize the genome against the rapid reversion that is observed following vaccination with Sabin OPV type 2 (mOPV2). Next-generation sequencing and a modified transgenic mouse neurovirulence test were applied to shed nOPV2 viruses from phase 1 and 2 studies and shed mOPV2 from a phase 4 study. The shed mOPV2 rapidly reverted in the primary attenuation site (domain V) and increased in virulence. In contrast, the shed nOPV2 viruses showed no evidence of reversion in domain V and limited or no increase in neurovirulence in mice. Based on these results and prior published data on safety, immunogenicity, and shedding, the nOPV2 viruses are promising alternatives to mOPV2 for outbreak responses.Rahnuma WahidLaina MercerAndrew MacadamSarah CarlyleLaura StephensJavier MartinKonstantin ChumakovMajid LaassriSvetlana PetrovskayaSaskia L. SmitsKoert J. StittelaarChris GastWilliam C. WeldonJennifer L. Konopka-AnstadtM. Steven OberstePierre Van DammeIlse De CosterRicardo RüttimannAnanda BandyopadhyayJohn KonzNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Rahnuma Wahid Laina Mercer Andrew Macadam Sarah Carlyle Laura Stephens Javier Martin Konstantin Chumakov Majid Laassri Svetlana Petrovskaya Saskia L. Smits Koert J. Stittelaar Chris Gast William C. Weldon Jennifer L. Konopka-Anstadt M. Steven Oberste Pierre Van Damme Ilse De Coster Ricardo Rüttimann Ananda Bandyopadhyay John Konz Assessment of genetic changes and neurovirulence of shed Sabin and novel type 2 oral polio vaccine viruses
description	Abstract Sabin-strain oral polio vaccines (OPV) can, in rare instances, cause disease in recipients and susceptible contacts or evolve to become circulating vaccine-derived strains with the potential to cause outbreaks. Two novel type 2 OPV (nOPV2) candidates were designed to stabilize the genome against the rapid reversion that is observed following vaccination with Sabin OPV type 2 (mOPV2). Next-generation sequencing and a modified transgenic mouse neurovirulence test were applied to shed nOPV2 viruses from phase 1 and 2 studies and shed mOPV2 from a phase 4 study. The shed mOPV2 rapidly reverted in the primary attenuation site (domain V) and increased in virulence. In contrast, the shed nOPV2 viruses showed no evidence of reversion in domain V and limited or no increase in neurovirulence in mice. Based on these results and prior published data on safety, immunogenicity, and shedding, the nOPV2 viruses are promising alternatives to mOPV2 for outbreak responses.
format	article
author	Rahnuma Wahid Laina Mercer Andrew Macadam Sarah Carlyle Laura Stephens Javier Martin Konstantin Chumakov Majid Laassri Svetlana Petrovskaya Saskia L. Smits Koert J. Stittelaar Chris Gast William C. Weldon Jennifer L. Konopka-Anstadt M. Steven Oberste Pierre Van Damme Ilse De Coster Ricardo Rüttimann Ananda Bandyopadhyay John Konz
author_facet	Rahnuma Wahid Laina Mercer Andrew Macadam Sarah Carlyle Laura Stephens Javier Martin Konstantin Chumakov Majid Laassri Svetlana Petrovskaya Saskia L. Smits Koert J. Stittelaar Chris Gast William C. Weldon Jennifer L. Konopka-Anstadt M. Steven Oberste Pierre Van Damme Ilse De Coster Ricardo Rüttimann Ananda Bandyopadhyay John Konz
author_sort	Rahnuma Wahid
title	Assessment of genetic changes and neurovirulence of shed Sabin and novel type 2 oral polio vaccine viruses
title_short	Assessment of genetic changes and neurovirulence of shed Sabin and novel type 2 oral polio vaccine viruses
title_full	Assessment of genetic changes and neurovirulence of shed Sabin and novel type 2 oral polio vaccine viruses
title_fullStr	Assessment of genetic changes and neurovirulence of shed Sabin and novel type 2 oral polio vaccine viruses
title_full_unstemmed	Assessment of genetic changes and neurovirulence of shed Sabin and novel type 2 oral polio vaccine viruses
title_sort	assessment of genetic changes and neurovirulence of shed sabin and novel type 2 oral polio vaccine viruses
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9baa83fb25b24bc98ad916e2a20f707d
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Assessment of genetic changes and neurovirulence of shed Sabin and novel type 2 oral polio vaccine viruses

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