Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, Colorado, USA.
Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
J Infect Dis. 2020 Jun 11;221(12):2050-2059. doi: 10.1093/infdis/jiaa049.
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.
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.
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.
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.
NCT03102034 and NCT03099291.
呼吸道合胞病毒（RSV）是导致严重儿科呼吸道疾病的主要病毒病原体，因此需要开发疫苗。活 RSV 疫苗 D46/NS2/N/ΔM2-2-HindIII 通过缺失 RSV RNA 调节蛋白 M2-2 而减毒，该疫苗以先前的候选疫苗 LID/ΔM2-2 为基础，但与 MEDI/ΔM2-2 存在显著差异，后者在 1 期的复制受到限制。
6-24 月龄 RSV 血清阴性儿童接受 1 次鼻内剂量（105 噬菌斑形成单位 [PFU] 的 D46/NS2/N/ΔM2-2-HindIII [n=21]或安慰剂 [n=11]），并在接下来的 RSV 季节监测疫苗脱落、不良反应、RSV 抗体反应以及 RSV 相关需要医疗干预的急性呼吸道疾病（RSV-MAARI）和抗体反应。
所有 21 名疫苗接种者均感染了疫苗；20 名（95%）出现疫苗脱落（免疫斑块法检测的中位峰值滴度为 3.5 log10 PFU/mL，聚合酶链反应检测的 6.1 log10 拷贝/mL）。血清 RSV 中和抗体和抗 RSV 融合免疫球蛋白 G 分别在 95%和 100%的疫苗接种者中增加≥4 倍。疫苗接种者（76%）和安慰剂接受者（18%）均出现轻度上呼吸道症状和/或发热。在 RSV 季节期间，2 名疫苗接种者和 4 名安慰剂接受者发生了 RSV-MAARI。3 名疫苗接种者在 RSV 季节后血清 RSV 中和抗体滴度增加≥4 倍，而没有 RSV-MAARI。
D46/NS2/N/ΔM2-2-HindIII 具有极好的感染性和免疫原性，为疫苗接种者引发了记忆反应，这鼓励进一步评估这种减毒策略。
NCT03102034 和 NCT03099291。
