Live-attenuated respiratory syncytial virus vaccine with deletion of RNA synthesis regulatory protein M2-2 and cold passage mutations is overattenuated

Coleen K. Cunningham; Ruth Karron; Petronella Muresan; Elizabeth J. McFarland; Charlotte Perlowski; Jennifer Libous; Bhagvanji Thumar; Devasena Gnanashanmugam; Jack Moye; Elizabeth Schappell; Emily Barr; Vivian Rexroad; Mariam Aziz; Jaime Deville; Richard Rutstein; Lijuan Yang; Cindy Luongo; Peter Collins; Ursula Buchholz

doi:10.1093/ofid/ofz212

Live-attenuated respiratory syncytial virus vaccine with deletion of RNA synthesis regulatory protein M2-2 and cold passage mutations is overattenuated

Coleen K. Cunningham
, Ruth Karron
, Petronella Muresan
, Elizabeth J. McFarland
, Charlotte Perlowski
, Jennifer Libous
, Bhagvanji Thumar
, Devasena Gnanashanmugam
, Jack Moye
, Elizabeth Schappell
, Emily Barr
, Vivian Rexroad
, Mariam Aziz
, Jaime Deville
, Richard Rutstein
, Lijuan Yang
, Cindy Luongo
, Peter Collins
, Ursula Buchholz

Nursing PhD Program

Duke University
Johns Hopkins University
Harvard University
University of Colorado Anschutz Medical Campus
FHI 360
National Institutes of Health
Rush University Medical Center
University of California at Los Angeles
Children's Hospital of Philadelphia

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

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 105 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 log10 PFU/mL by quantitative culture and 4.5 log10 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%).

Original language	English
Article number	ofz212
Journal	Open Forum Infectious Diseases
Volume	6
Issue number	6
DOIs	https://doi.org/10.1093/ofid/ofz212
State	Published - Jun 3 2019

Keywords

Immunogenicity
Live-attenuated viral vaccine
Neutralizing antibodies
Pediatric RSV vaccine
RNA regulatory protein M2-2
Respiratory syncytial virus

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10.1093/ofid/ofz212

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Cunningham, C. K., Karron, R., Muresan, P., McFarland, E. J., Perlowski, C., Libous, J., Thumar, B., Gnanashanmugam, D., Moye, J., Schappell, E., Barr, E., Rexroad, V., Aziz, M., Deville, J., Rutstein, R., Yang, L., Luongo, C., Collins, P., & Buchholz, U. (2019). Live-attenuated respiratory syncytial virus vaccine with deletion of RNA synthesis regulatory protein M2-2 and cold passage mutations is overattenuated. Open Forum Infectious Diseases, 6(6), Article ofz212. https://doi.org/10.1093/ofid/ofz212

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title = "Live-attenuated respiratory syncytial virus vaccine with deletion of RNA synthesis regulatory protein M2-2 and cold passage mutations is overattenuated",

abstract = "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 105 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 log10 PFU/mL by quantitative culture and 4.5 log10 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\%).",

keywords = "Immunogenicity, Live-attenuated viral vaccine, Neutralizing antibodies, Pediatric RSV vaccine, RNA regulatory protein M2-2, Respiratory syncytial virus",

author = "Cunningham, \{Coleen K.\} and Ruth Karron and Petronella Muresan and McFarland, \{Elizabeth J.\} and Charlotte Perlowski and Jennifer Libous and Bhagvanji Thumar and Devasena Gnanashanmugam and Jack Moye and Elizabeth Schappell and Emily Barr and Vivian Rexroad and Mariam Aziz and Jaime Deville and Richard Rutstein and Lijuan Yang and Cindy Luongo and Peter Collins and Ursula Buchholz",

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year = "2019",

month = jun,

day = "3",

doi = "10.1093/ofid/ofz212",

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Cunningham, CK, Karron, R, Muresan, P, McFarland, EJ, Perlowski, C, Libous, J, Thumar, B, Gnanashanmugam, D, Moye, J, Schappell, E, Barr, E, Rexroad, V, Aziz, M, Deville, J, Rutstein, R, Yang, L, Luongo, C, Collins, P & Buchholz, U 2019, 'Live-attenuated respiratory syncytial virus vaccine with deletion of RNA synthesis regulatory protein M2-2 and cold passage mutations is overattenuated', Open Forum Infectious Diseases, vol. 6, no. 6, ofz212. https://doi.org/10.1093/ofid/ofz212

TY - JOUR

T1 - Live-attenuated respiratory syncytial virus vaccine with deletion of RNA synthesis regulatory protein M2-2 and cold passage mutations is overattenuated

AU - Cunningham, Coleen K.

AU - Karron, Ruth

AU - Muresan, Petronella

AU - McFarland, Elizabeth J.

AU - Perlowski, Charlotte

AU - Libous, Jennifer

AU - Thumar, Bhagvanji

AU - Gnanashanmugam, Devasena

AU - Moye, Jack

AU - Schappell, Elizabeth

AU - Barr, Emily

AU - Rexroad, Vivian

AU - Aziz, Mariam

AU - Deville, Jaime

AU - Rutstein, Richard

AU - Yang, Lijuan

AU - Luongo, Cindy

AU - Collins, Peter

AU - Buchholz, Ursula

PY - 2019/6/3

Y1 - 2019/6/3

N2 - 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 105 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 log10 PFU/mL by quantitative culture and 4.5 log10 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%).

AB - 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 105 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 log10 PFU/mL by quantitative culture and 4.5 log10 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%).

KW - Immunogenicity

KW - Live-attenuated viral vaccine

KW - Neutralizing antibodies

KW - Pediatric RSV vaccine

KW - RNA regulatory protein M2-2

KW - Respiratory syncytial virus

UR - https://www.scopus.com/pages/publications/85068513984

U2 - 10.1093/ofid/ofz212

DO - 10.1093/ofid/ofz212

M3 - Article

AN - SCOPUS:85068513984

SN - 2328-8957

VL - 6

JO - Open Forum Infectious Diseases

JF - Open Forum Infectious Diseases

IS - 6

M1 - ofz212

ER -

Live-attenuated respiratory syncytial virus vaccine with deletion of RNA synthesis regulatory protein M2-2 and cold passage mutations is overattenuated

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Keywords

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