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Live-Attenuated Respiratory Syncytial Virus Vaccine With Deletion of RNA Synthesis Regulatory Protein M2-2 and Cold Passage Mutations Is Overattenuated

BACKGROUND: The live respiratory syncytial virus (RSV) candidate vaccine LIDcpΔM2-2 is attenuated through deletion of M2-2 and 5 cold-passage mutations. METHODS: RSV-seronegative children aged 6–24 months received a single intranasal dose of 10(5) plaque-forming units (PFU) of LIDcpΔM2-2 or placebo....

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Autores principales: Cunningham, Coleen K, Karron, Ruth, Muresan, Petronella, McFarland, Elizabeth J, Perlowski, Charlotte, Libous, Jennifer, Thumar, Bhagvanji, Gnanashanmugam, Devasena, Moye, Jack, Schappell, Elizabeth, Barr, Emily, Rexroad, Vivian, Aziz, Mariam, Deville, Jaime, Rutstein, Richard, Yang, Lijuan, Luongo, Cindy, Collins, Peter, Buchholz, Ursula
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559275/
https://www.ncbi.nlm.nih.gov/pubmed/31211158
http://dx.doi.org/10.1093/ofid/ofz212
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author Cunningham, Coleen K
Karron, Ruth
Muresan, Petronella
McFarland, Elizabeth J
Perlowski, Charlotte
Libous, Jennifer
Thumar, Bhagvanji
Gnanashanmugam, Devasena
Moye, Jack
Schappell, Elizabeth
Barr, Emily
Rexroad, Vivian
Aziz, Mariam
Deville, Jaime
Rutstein, Richard
Yang, Lijuan
Luongo, Cindy
Collins, Peter
Buchholz, Ursula
author_facet Cunningham, Coleen K
Karron, Ruth
Muresan, Petronella
McFarland, Elizabeth J
Perlowski, Charlotte
Libous, Jennifer
Thumar, Bhagvanji
Gnanashanmugam, Devasena
Moye, Jack
Schappell, Elizabeth
Barr, Emily
Rexroad, Vivian
Aziz, Mariam
Deville, Jaime
Rutstein, Richard
Yang, Lijuan
Luongo, Cindy
Collins, Peter
Buchholz, Ursula
author_sort Cunningham, Coleen K
collection PubMed
description BACKGROUND: The live respiratory syncytial virus (RSV) candidate vaccine LIDcpΔM2-2 is attenuated through deletion of M2-2 and 5 cold-passage mutations. METHODS: RSV-seronegative children aged 6–24 months received a single intranasal dose of 10(5) plaque-forming units (PFU) of LIDcpΔM2-2 or placebo. RSV serum antibodies, vaccine infectivity, and reactogenicity were assessed. RESULTS: Four of 11 (36%) vaccinees shed vaccine virus with median peak titers of 1.6 log(10) PFU/mL by quantitative culture and 4.5 log(10) copies/mL by polymerase chain reaction; 45% had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms or fever were common in vaccinees (64%) and placebo recipients (6/6, 100%). CONCLUSIONS: RSV LIDcpΔM2-2 is overattenuated. Clinical Trial Numbers. NCT02890381, NCT02948127.
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spelling pubmed-65592752019-06-17 Live-Attenuated Respiratory Syncytial Virus Vaccine With Deletion of RNA Synthesis Regulatory Protein M2-2 and Cold Passage Mutations Is Overattenuated Cunningham, Coleen K Karron, Ruth Muresan, Petronella McFarland, Elizabeth J Perlowski, Charlotte Libous, Jennifer Thumar, Bhagvanji Gnanashanmugam, Devasena Moye, Jack Schappell, Elizabeth Barr, Emily Rexroad, Vivian Aziz, Mariam Deville, Jaime Rutstein, Richard Yang, Lijuan Luongo, Cindy Collins, Peter Buchholz, Ursula Open Forum Infect Dis Brief Report BACKGROUND: The live respiratory syncytial virus (RSV) candidate vaccine LIDcpΔM2-2 is attenuated through deletion of M2-2 and 5 cold-passage mutations. METHODS: RSV-seronegative children aged 6–24 months received a single intranasal dose of 10(5) plaque-forming units (PFU) of LIDcpΔM2-2 or placebo. RSV serum antibodies, vaccine infectivity, and reactogenicity were assessed. RESULTS: Four of 11 (36%) vaccinees shed vaccine virus with median peak titers of 1.6 log(10) PFU/mL by quantitative culture and 4.5 log(10) copies/mL by polymerase chain reaction; 45% had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms or fever were common in vaccinees (64%) and placebo recipients (6/6, 100%). CONCLUSIONS: RSV LIDcpΔM2-2 is overattenuated. Clinical Trial Numbers. NCT02890381, NCT02948127. Oxford University Press 2019-05-06 /pmc/articles/PMC6559275/ /pubmed/31211158 http://dx.doi.org/10.1093/ofid/ofz212 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Brief Report
Cunningham, Coleen K
Karron, Ruth
Muresan, Petronella
McFarland, Elizabeth J
Perlowski, Charlotte
Libous, Jennifer
Thumar, Bhagvanji
Gnanashanmugam, Devasena
Moye, Jack
Schappell, Elizabeth
Barr, Emily
Rexroad, Vivian
Aziz, Mariam
Deville, Jaime
Rutstein, Richard
Yang, Lijuan
Luongo, Cindy
Collins, Peter
Buchholz, Ursula
Live-Attenuated Respiratory Syncytial Virus Vaccine With Deletion of RNA Synthesis Regulatory Protein M2-2 and Cold Passage Mutations Is Overattenuated
title Live-Attenuated Respiratory Syncytial Virus Vaccine With Deletion of RNA Synthesis Regulatory Protein M2-2 and Cold Passage Mutations Is Overattenuated
title_full Live-Attenuated Respiratory Syncytial Virus Vaccine With Deletion of RNA Synthesis Regulatory Protein M2-2 and Cold Passage Mutations Is Overattenuated
title_fullStr Live-Attenuated Respiratory Syncytial Virus Vaccine With Deletion of RNA Synthesis Regulatory Protein M2-2 and Cold Passage Mutations Is Overattenuated
title_full_unstemmed Live-Attenuated Respiratory Syncytial Virus Vaccine With Deletion of RNA Synthesis Regulatory Protein M2-2 and Cold Passage Mutations Is Overattenuated
title_short Live-Attenuated Respiratory Syncytial Virus Vaccine With Deletion of RNA Synthesis Regulatory Protein M2-2 and Cold Passage Mutations Is Overattenuated
title_sort live-attenuated respiratory syncytial virus vaccine with deletion of rna synthesis regulatory protein m2-2 and cold passage mutations is overattenuated
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559275/
https://www.ncbi.nlm.nih.gov/pubmed/31211158
http://dx.doi.org/10.1093/ofid/ofz212
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