2区 · 医学
Article
作者: Cielo, Mikhaela ; Libous, Jennifer ; Aziz, Mariam ; Fearn, Laura ; Moye, Jack ; Buchholz, Ursula J ; Beneri, Christy ; McFarland, Elizabeth J ; Karron, Ruth A ; Cunningham, Coleen K ; Barr, Emily ; Muresan, Petronella ; Wiznia, Andrew ; Spector, Stephen A ; Luongo, Cindy ; Schappell, Elizabeth ; Rexroad, Vivian ; Collins, Peter ; Perlowski, Charlotte ; Thumar, Bhagvanji ; Gnanashanmugam, Devasena
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.