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

Journal Article (Journal Article;Multicenter Study)

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 [nā€…=ā€…21] or placebo [nā€…=ā€…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.

Full Text

Duke Authors

Cited Authors

  • McFarland, EJ; Karron, RA; Muresan, P; Cunningham, CK; Perlowski, C; Libous, J; Oliva, J; Jean-Philippe, P; Moye, J; Schappell, E; Barr, E; Rexroad, V; Fearn, L; Cielo, M; Wiznia, A; Deville, JG; Yang, L; Luongo, C; Collins, PL; Buchholz, UJ

Published Date

  • June 11, 2020

Published In

Volume / Issue

  • 221 / 12

Start / End Page

  • 2050 - 2059

PubMed ID

  • 32006006

Pubmed Central ID

  • PMC7289559

Electronic International Standard Serial Number (EISSN)

  • 1537-6613

Digital Object Identifier (DOI)

  • 10.1093/infdis/jiaa049


  • eng

Conference Location

  • United States