August Allison, Glenn Gregory M, Kpamegan Eloi, Hickman Somia P, Jani Dewal, Lu Hanxin, Thomas D Nigel, Wen Judy, Piedra Pedro A, Fries Louis F
Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA.
Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Vaccine. 2017 Jun 27;35(30):3749-3759. doi: 10.1016/j.vaccine.2017.05.045. Epub 2017 Jun 1.
Respiratory syncytial virus (RSV) causes significant morbidity and mortality in infants. We are developing an RSV fusion (F) protein nanoparticle vaccine for immunization of third trimester pregnant women to passively protect infants through transfer of RSV-specific maternal antibodies. The present trial was performed to assess the immunogenicity and safety of several formulations of RSV F vaccine in 1-dose or 2-dose schedules.
Placebo, or vaccine with 60μg or 120μg RSV F protein and 0.2, 0.4, or 0.8mg aluminum, were administered intramuscularly on Days 0 and 28 to healthy women 18-35years old. Immunogenicity was assessed from Days 0 through 91 based on anti-F IgG and palivizumab-competitive antibody (PCA) by ELISA, and RSV A and B neutralizing antibodies by microneutralization (MN) assay. Solicited adverse events were collected through Day 7 and unsolicited adverse events through Day 91.
All formulations were well-tolerated, with no treatment-related serious adverse events. Anti-F IgG and PCA responses were correlated and increased after both doses, while MN increased significantly only after the first dose, then plateaued. The timeliest and most robust antibody responses followed one dose of 120μg RSV F protein and 0.4mg aluminum, but persistence through 91days was modestly (∼25%) superior following two doses of 60μg RSV F protein and 0.8mg aluminum. Western blot analysis showed RSV infections in active vaccinees were reduced by 52% overall (p=0.009 overall) over the Day 0 through 90 period.
RSV F nanoparticle vaccine formulations were well tolerated and immunogenic. The optimal combination of convenience and rapid response for immunization in the third trimester occurred with 120μg RSV F and 0.4mg aluminum, which achieved peak immune responses in 14days and sufficient persistence through 91days to allow for passive transfer of IgG antibodies to the fetus. NCT01960686.
呼吸道合胞病毒（RSV）可导致婴儿出现严重发病和死亡情况。我们正在研发一种RSV融合（F）蛋白纳米颗粒疫苗，用于对孕晚期孕妇进行免疫接种，以通过母婴特异性抗体的传递来被动保护婴儿。本试验旨在评估RSV F疫苗几种配方在1剂或2剂接种方案下的免疫原性和安全性。
在第0天和第28天，对18 - 35岁的健康女性肌肉注射安慰剂，或含有60μg或120μg RSV F蛋白以及0.2mg、0.4mg或0.8mg铝佐剂的疫苗。在第0天至第91天期间，通过酶联免疫吸附测定（ELISA）检测抗F IgG和帕利珠单抗竞争性抗体（PCA）来评估免疫原性，通过微量中和（MN）试验检测RSV A和B中和抗体。在第7天收集主动报告的不良事件，在第91天收集非主动报告的不良事件。
所有配方的耐受性良好，未出现与治疗相关的严重不良事件。抗F IgG和PCA反应相关，两剂接种后均有所增加，而MN仅在首剂接种后显著增加，随后趋于平稳。一剂120μg RSV F蛋白加0.4mg铝佐剂接种后抗体反应出现得最早且最强，但两剂60μg RSV F蛋白加0.8mg铝佐剂接种后抗体在91天内的持续时间适度延长（约25%）。蛋白质免疫印迹分析显示，在第0天至第90天期间，主动接种疫苗者的RSV感染总体减少了52%（总体p = 0.009）。
RSV F纳米颗粒疫苗配方耐受性良好且具有免疫原性。孕晚期免疫接种时，便利性和快速反应的最佳组合是120μg RSV F加0.4mg铝佐剂，该组合在14天内达到免疫反应峰值，且在91天内有足够的持续时间，使IgG抗体能够被动转移至胎儿。临床试验注册号：NCT01960686。
