Live Respiratory Syncytial Virus Attenuated by M2-2 Deletion and Stabilized Temperature Sensitivity Mutation 1030s Is a Promising Vaccine Candidate in Children

Elizabeth J. McFarland, Ruth A. Karron, Petronella Muresan, Coleen K. Cunningham, Jennifer Libous, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, Jack Moye, Elizabeth Schappell, Emily Barr, Vivian Rexroad, Laura Fearn, Stephen A. Spector, Mariam Aziz, Mikhaela Cielo, Christy Beneri, Andrew Wiznia, Cindy Luongo, Peter CollinsUrsula J. Buchholz

Research output: Contribution to journalArticle

Abstract

Background: The safety and immunogenicity of live respiratory syncytial virus (RSV) candidate vaccine, LID/ΔM2-2/1030s, with deletion of RSV ribonucleic acid synthesis regulatory protein M2-2 and genetically stabilized temperature-sensitivity mutation 1030s in the RSV polymerase protein was evaluated in RSV-seronegative children. Methods: Respiratory syncytial virus-seronegative children ages 6-24 months received 1 intranasal dose of 105 plaque-forming units (PFU) of LID/ΔM2-2/1030s (n = 21) or placebo (n = 11). The RSV serum antibodies, vaccine shedding, and reactogenicity were assessed. During the following RSV season, medically attended acute respiratory illness (MAARI) and pre- and postsurveillance serum antibody titers were monitored. Results: Eighty-five percent of vaccinees shed LID/ΔM2-2/1030s vaccine (median peak nasal wash titers: 3.1 log10 PFU/mL by immunoplaque assay; 5.1 log10 copies/mL by reverse-transcription quantitative polymerase chain reaction) and had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms and fever were common (60% vaccinees and 27% placebo recipients). One vaccinee had grade 2 wheezing with rhinovirus but without concurrent LID/ΔM2-2/1030s shedding. Five of 19 vaccinees had ≥4-fold increases in antibody titers postsurveillance without RSV-MAARI, indicating anamnestic responses without significant illness after infection with community-acquired RSV. Conclusions: LID/ΔM2-2/1030s had excellent infectivity without evidence of genetic instability, induced durable immunity, and primed for anamnestic antibody responses, making it an attractive candidate for further evaluation.

Original languageEnglish (US)
Pages (from-to)534-543
Number of pages10
JournalJournal of Infectious Diseases
Volume221
Issue number4
DOIs
StatePublished - Feb 3 2020

Keywords

  • live-attenuated viral vaccine
  • neutralizing antibodies
  • pediatric RSV vaccine
  • respiratory syncytial virus (RSV)
  • RNA regulatory protein M2-2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    McFarland, E. J., Karron, R. A., Muresan, P., Cunningham, C. K., Libous, J., Perlowski, C., Thumar, B., Gnanashanmugam, D., Moye, J., Schappell, E., Barr, E., Rexroad, V., Fearn, L., Spector, S. A., Aziz, M., Cielo, M., Beneri, C., Wiznia, A., Luongo, C., ... Buchholz, U. J. (2020). Live Respiratory Syncytial Virus Attenuated by M2-2 Deletion and Stabilized Temperature Sensitivity Mutation 1030s Is a Promising Vaccine Candidate in Children. Journal of Infectious Diseases, 221(4), 534-543. https://doi.org/10.1093/infdis/jiz603