Genetic and phenotypic stability of poliovirus shed from infants who received novel type 2 or Sabin type 2 oral poliovirus vaccines in Panama: an analysis of two clinical trials.
| Autor: | Wahid R; Center for Vaccine Innovation and Access, PATH, Seattle, WA, USA., Mercer LD; Center for Vaccine Innovation and Access, PATH, Seattle, WA, USA., De Leon T; Hospital Materno Infantil José Domingo De Obaldía, David, Panama; CEVAXIN, Centro de Vacunación e Investigación, Panama City, Panama., DeAntonio R; CEVAXIN, Centro de Vacunación e Investigación, Panama City, Panama., Sáez-Llorens X; CEVAXIN, Centro de Vacunación e Investigación, Panama City, Panama; Department of Infectious Diseases, Hospital del Niño Dr José Renán Esquivel and Sistema Nacional de Investigación at Secretaria Nacional de Ciencia y Tecnologia, Panama City, Panama., Macadam A; Division of Virology, National Institute for Biological Standards and Control, South Mimms, UK., Chumakov K; Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA; Global Virus Network Center of Excellence, Baltimore, MD, USA., Strating J; Viroclinics Biosciences, Rotterdam, Netherlands., Koel B; Viroclinics Xplore, Viroclinics Biosciences, Rotterdam, Netherlands., Konopka-Anstadt JL; Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA., Oberste MS; Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA., Burns CC; Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA., Andino R; Department of Microbiology and Immunology, University of California, San Francisco, CA, USA., Tritama E; Research and Development Division, PT Bio Farma, Bandung, West Java, Indonesia., Bandyopadhyay AS; Bill & Melinda Gates Foundation, Seattle, WA, USA., Aguirre G; Fighting Infectious Diseases in Emerging Countries, Miami, FL, USA., Rüttimann R; Fighting Infectious Diseases in Emerging Countries, Miami, FL, USA., Gast C; Center for Vaccine Innovation and Access, PATH, Seattle, WA, USA., Konz JO; Center for Vaccine Innovation and Access, PATH, Seattle, WA, USA. Electronic address: jkonz@path.org. |
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| Jazyk: | angličtina |
| Zdroj: | The Lancet. Microbe [Lancet Microbe] 2022 Dec; Vol. 3 (12), pp. e912-e921. Date of Electronic Publication: 2022 Nov 01. |
| DOI: | 10.1016/S2666-5247(22)00254-3 |
| Abstrakt: | Background: Sabin strains used in oral poliovirus vaccines (OPV) can revert to virulence and, in rare instances, cause disease or generate vaccine-derived strains leading to outbreaks in areas of low immunisation coverage. A novel OPV2 (nOPV2) was designed to stabilise the viral genome against reversion and reduce recombination events that might lead to virulent strains. In this study, we evaluated the genetic and phenotypic stability of shed poliovirus following administration of one dose of monovalent OPV2 (mOPV2) or nOPV2 to infants aged 18-22 weeks. Methods: In two similarly designed clinical trials (NCT02521974 and NCT03554798) conducted in Panama, infants aged 18-22-weeks, after immunisation with three doses of bivalent OPV (types 1 and 3) and one dose of inactivated poliovirus vaccine, were administered one or two doses of mOPV2 or nOPV2. In this analysis of two clinical trials, faecally shed polioviruses following one dose of mOPV2 or nOPV2 were isolated from stools meeting predetermined criteria related to sample timing and viral presence and quantity and assessed for nucleotide polymorphisms using next-generation sequencing. A transgenic mouse neurovirulence test was adapted to assess the effect of the possible phenotypic reversion of shed mOPV2 and nOPV2 with a logistic regression model. Findings: Of the 91 eligible samples, 86 were able to be sequenced, with 72 evaluated in the transgenic mouse assay. Sabin-2 poliovirus reverts rapidly at nucleotide 481, the primary attenuation site in domain V of the 5' untranslated region of the genome. There was no evidence of neurovirulence-increasing polymorphisms in domain V of shed nOPV2. Reversion of shed Sabin-2 virus corresponded with unadjusted paralysis rates of 47·6% at the 4 log Interpretation: The data indicate increased genetic stability of domain V of nOPV2 relative to mOPV2, with significantly lower neurovirulence of shed nOPV2 virus compared with shed mOPV2. While this vaccine is currently being deployed under an emergency use listing, the data on the genetic stability of nOPV2 will support further regulatory and policy decision-making regarding use of nOPV2 in outbreak responses. Funding: Bill & Melinda Gates Foundation. Competing Interests: Declaration of interests We declare no competing interests. The National Institute for Biological Standards and Control, University of California, San Francisco, claim intellectual property rights associated with the nOPV2-c1. ET works for the manufacturer of nOPV2. JS and BK are employees of Viroclinics, which is paid by PATH for the conduct of next-generation sequencing and mouse neurovirulence tests. ASB was an employee of the study funder and was involved in study design and writing of the report but had no role in data collection or analysis. (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.) |
| Databáze: | MEDLINE |
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