Modeling maternal fetal RSV F vaccine induced antibody transfer in guinea pigs
Modeling maternal fetal RSV F vaccine induced antibody transfer in guinea pigs
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DOI：
10.1016/j.vaccine.2015.08.039
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发表时间：
2015-11-25
期刊：
影响因子：
5.5
通讯作者：
Flyer, David
中科院分区：
文献类型：
--
作者：
Glenn, Gregory M.;Fries, Louis F.;Flyer, David
背景：经胎盘转移抗体介导的母体免疫对新生儿和婴幼儿的保护作用正在接受RSV重组F纳米颗粒疫苗(RSV F疫苗)在妊娠晚期妇女中的评估。由于豚鼠和人的胎盘结构相似，采用豚鼠模型来评估RSV F疫苗在妊娠母猪中的免疫原性，并比较它们的瞳孔中RSV特异性母体抗体水平。方法：30只假定怀孕的豚鼠在妊娠第25天和46天分别用安慰剂(PBS)、30 mgRSV F或30 mgRSV F+400 mg磷酸铝免疫。于分娩/分娩时(母猪/仔猪)、产后15天和产后30天(仔猪)分别检测血清中抗F-Ig G、Palivizumab竞争性抗体(PCA)和RSV/A微量中和试验(MN)。结果：对照组和疫苗接种组的妊娠率和死产率相似。该疫苗在母猪体内诱导了高水平的抗F-Ig G、PCA和MN，其中在佐剂接种者中的水平最高。胎盘转移到仔鼠与母体抗体水平成正比，所有免疫指标都观察到浓度效应。结论：RSV F疫苗对妊娠豚鼠是安全的和免疫原性的，并支持强大的经胎盘抗体转移到仔鼠。即使在母体抗体水平较高的情况下，也能观察到幼崽体内抗体的相对浓度。豚鼠可能是母体免疫候选疫苗临床前评估的一个重要的安全性和免疫原性模型。(C)2015年提交人。爱思唯尔有限公司出版。
Background: Protection of newborns and young infants against RSV disease via maternal immunization mediated by transplacental transfer of antibodies is under evaluation in third-trimester pregnant women with the RSV recombinant F nanoparticle vaccine (RSV F vaccine). Since the hemichorial placental architecture in guinea pigs and humans is similar, the guinea pig model was employed to assess RSV F vaccine immunogenicity in pregnant sows and to compare RSV-specific maternal antibody levels in their pups.Methods: Thirty (30) presumptive pregnant guinea pigs were immunized on gestational day 25 and 46 with placebo (PBS), 30 mu g RSV F, or 30 mu g RSV F + 400 mu g aluminum phosphate. Sera at delivery/birth (sows/pups) and 15 and 30 days post-partum (pups) were analyzed for the presence of anti-F IgG, palivizumab-competitive antibody (PCA) and RSV/A microneutralization (MN).Results: The rates of pregnancy and stillbirth were similar between controls and vaccinees. The vaccine induced high levels of anti-F IgG, PCA and MN in sows, with the highest levels observed in adjuvanted vaccinees. Placental transfer to pups was proportional to the maternal antibody levels, with concentration effects observed for all immune measures.Conclusions: The RSV F vaccine was safe and immunogenic in pregnant guinea pigs and supported robust transplacental antibody transfer to their pups. Relative concentration of antibodies in the pups was observed even in the presence of high levels of maternal antibody. Guinea pigs may be an important safety and immunogenicity model for preclinical assessment of candidate vaccines for maternal immunization. (C) 2015 The Authors. Published by Elsevier Ltd.