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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Article numberofz212
JournalOpen Forum Infectious Diseases
Volume6
Issue number6
DOIs
StatePublished - Jun 3 2019

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology

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