Article
作者: McFarland, Elizabeth J ; Aziz, Mariam ; Deville, Jaime G ; Cielo, Mikhaela ; Yang, Lijuan ; Libous, Jennifer ; Barr, Emily ; Schappell, Elizabeth ; Cunningham, Coleen K ; Luongo, Cindy ; Karron, Ruth A ; Muresan, Petronella ; Jean-Philippe, Patrick ; Kelly, Matthew S ; Rexroad, Vivian ; Moye, Jack ; Buchholz, Ursula J ; Collins, Peter L ; Chadwick, Ellen G ; Paul, Mary ; Perlowski, Charlotte ; Johnston, Benjamin ; Oliva, Jennifer
Background:This United States-based study compared 2 candidate vaccines: RSV/ΔNS2/Δ1313/I1314L, attenuated by NS2 gene-deletion and temperature-sensitivity mutation in the polymerase gene; and RSV/276, attenuated by M2-2 deletion.
Methods:RSV-seronegative children aged 6–24 months received RSV/ΔNS2/Δ1313/I1314L (106 plaque-forming units [PFU]), RSV/276 (105 PFU), or placebo intranasally. Participants were monitored for vaccine shedding, reactogenicity, and RSV serum antibodies, and followed over the subsequent RSV season.
Results:Enrollment occurred September 2017 to October 2019. During 28 days postinoculation, upper respiratory illness and/or fever occurred in 64% of RSV/ΔNS2/Δ1313/I1314L, 84% of RSV/276, and 58% of placebo recipients. Symptoms were generally mild. Cough was more common in RSV/276 recipients than RSV/ΔNS2/Δ1313/I1314L (48% vs 12%; P = .012) or placebo recipients (17%; P = .084). There were no lower respiratory illness or serious adverse events. Eighty-eight and 96% of RSV/ΔNS2/Δ1313/I1314L and RSV/276 recipients were infected with vaccine (shed vaccine and/or had ≥4-fold rises in RSV antibodies). Serum RSV-neutralizing titers and anti-RSV F IgG titers increased ≥4-fold in 60% and 92% of RSV/ΔNS2/Δ1313/I1314L and RSV/276 vaccinees, respectively. Exposure to community RSV during the subsequent winter was associated with strong anamnestic RSV-antibody responses.
Conclusions:Both vaccines had excellent infectivity and were well tolerated. RSV/276 induced an excess of mild cough. Both vaccines were immunogenic and primed for strong anamnestic responses.
Clinical Trials Registration:NCT03227029 and NCT03422237.