2区 · 医学
Article
作者: Deville, Jaime G ; Cielo, Mikhaela ; Buchholz, Ursula J ; Libous, Jennifer ; Fearn, Laura ; Moye, Jack ; McFarland, Elizabeth J ; Karron, Ruth A ; Cunningham, Coleen K ; Barr, Emily ; Collins, Peter L ; Muresan, Petronella ; Jean-Philippe, Patrick ; Oliva, Jennifer ; Perlowski, Charlotte ; Luongo, Cindy ; Schappell, Elizabeth ; Wiznia, Andrew ; Rexroad, Vivian ; Yang, Lijuan
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.