Glenn Gregory M, Fries Louis F, Smith Gale, Kpamegan Eloi, Lu Hanxin, Guebre-Xabier Mimi, Hickman Somia P, Flyer David
Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA.
Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA.
Vaccine. 2015 Nov 25;33(47):6488-92. doi: 10.1016/j.vaccine.2015.08.039. Epub 2015 Aug 28.
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.
Thirty (30) presumptive pregnant guinea pigs were immunized on gestational day 25 and 46 with placebo (PBS), 30μg RSV F, or 30μg RSV F+400μg 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).
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.
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.
通过抗体经胎盘转移介导的母体免疫来保护新生儿和幼儿免受呼吸道合胞病毒（RSV）疾病侵害，这一方法正在接受使用RSV重组F纳米颗粒疫苗（RSV F疫苗）的孕晚期孕妇的评估。由于豚鼠和人类的半绒毛膜胎盘结构相似，因此采用豚鼠模型来评估RSV F疫苗在怀孕母猪中的免疫原性，并比较其幼崽中RSV特异性母体抗体水平。
30只假定怀孕的豚鼠在妊娠第25天和第46天分别用安慰剂（PBS）、30μg RSV F或30μg RSV F + 400μg磷酸铝进行免疫。分析分娩/出生时（母猪/幼崽）以及产后15天和30天（幼崽）的血清中抗F IgG、帕利珠单抗竞争抗体（PCA）和RSV/A微量中和（MN）的存在情况。
对照组和接种疫苗组之间的妊娠率和死产率相似。该疫苗在母猪中诱导产生了高水平的抗F IgG、PCA和MN，在佐剂疫苗接种组中观察到的水平最高。向幼崽的胎盘转移与母体抗体水平成正比，所有免疫指标均观察到浓度效应。
RSV F疫苗在怀孕豚鼠中是安全且具有免疫原性的，并支持向其幼崽进行强大的经胎盘抗体转移。即使在母体抗体水平较高的情况下，也观察到了幼崽中抗体的相对浓度。豚鼠可能是用于母体免疫候选疫苗临床前评估的重要安全性和免疫原性模型。
