Live-Attenuated Respiratory Syncytial Virus Vaccine with M2-2 Deletion and with Small Hydrophobic Noncoding Region Is Highly Immunogenic in Children

Elizabeth J. McFarland, Ruth A. Karron, Petronella Muresan, Coleen K. Cunningham, Charlotte Perlowski, Jennifer Libous, Jennifer Oliva, Patrick Jean-Philippe, Jack Moye, Elizabeth Schappell, Emily Barr, Vivian Rexroad, Laura Fearn, Mikhaela Cielo, Andrew Wiznia, Jaime G. Deville, Lijuan Yang, Cindy Luongo, Peter L. Collins, Ursula J. Buchholz

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Background: Respiratory syncytial virus (RSV) is the leading viral cause of severe pediatric respiratory illness, and vaccines are needed. Live RSV vaccine D46/NS2/N/ΔM2-2-HindIII, attenuated by deletion of the RSV RNA regulatory protein M2-2, is based on previous candidate LID/ΔM2-2 but incorporates prominent differences from MEDI/ΔM2-2, which was more restricted in replication in phase 1. Methods: RSV-seronegative children aged 6-24 months received 1 intranasal dose (105 plaque-forming units [PFUs] of D46/NS2/N/ΔM2-2-HindIII [n=21] or placebo [n=11]) and were monitored for vaccine shedding, reactogenicity, RSV-antibody responses and RSV-associated medically attended acute respiratory illness (RSV-MAARI) and antibody responses during the following RSV season. Results: All 21 vaccinees were infected with vaccine; 20 (95%) shed vaccine (median peak titer, 3.5 log10 PFUs/mL with immunoplaque assay and 6.1 log10 copies/mL with polymerase chain reaction). Serum RSV-neutralizing antibodies and anti-RSV fusion immunoglobulin G increased ≥4-fold in 95% and 100% of vaccines, respectively. Mild upper respiratory tract symptoms and/or fever occurred in vaccinees (76%) and placebo recipients (18%). Over the RSV season, RSV-MAARI occurred in 2 vaccinees and 4 placebo recipients. Three vaccinees had ≥4-fold increases in serum RSV-neutralizing antibody titers after the RSV season without RSV-MAARI. Conclusions: D46/NS2/N/ΔM2-2-HindIII had excellent infectivity and immunogenicity and primed vaccine recipients for anamnestic responses, encouraging further evaluation of this attenuation strategy. Clinical Trials Registration: NCT03102034 and NCT03099291.

Original languageEnglish (US)
Pages (from-to)2050-2059
Number of pages10
JournalJournal of Infectious Diseases
Issue number12
StatePublished - Jun 11 2020


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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases


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