School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA.
Viruses. 2017 Sep 21;9(10):265. doi: 10.3390/v9100265.
Current measles vaccines suffer from poor effectiveness in young infants due primarily to the inhibitory effect of residual maternal immunity on vaccine responses. The development of a measles vaccine that resists such passive immunity would strongly contribute to the stalled effort toward measles eradication. In this concise communication, we show that a measles virus (MV) with enhanced hemagglutinin (H) expression and incorporation, termed MVvac2-H2, retained its enhanced immunogenicity, previously established in older mice, when administered to very young, genetically modified, MV-susceptible mice in the presence of passive anti-measles immunity. This immunity level mimics the sub-neutralizing immunity prevalent in infants too young to be vaccinated. Additionally, toward a more physiological small animal model of maternal anti-measles immunity interference, we document vertical transfer of passive anti-MV immunity in genetically-modified, MV susceptible mice and show in this physiological model a better MVvac2-H2 immunogenic profile than that of the parental vaccine strain. In sum, these data support the notion that enhancing MV hemagglutinin incorporation can circumvent in vivo neutralization. This strategy merits additional exploration as an alternative pediatric measles vaccine.
目前的麻疹疫苗在婴幼儿中的效果不佳，主要是由于母体免疫力对疫苗反应的抑制作用。开发一种能够抵抗这种被动免疫的麻疹疫苗，将有力地推动麻疹消除工作的停滞不前。在本简明通讯中，我们表明，一种增强了血凝素（H）表达和结合的麻疹病毒（MV），称为 MVvac2-H2，在存在被动抗麻疹免疫的情况下，当给予非常年幼的、遗传修饰的、对 MV 易感的小鼠时，保留了其在老年小鼠中建立的增强免疫原性。这种免疫水平模拟了在太小而不能接种疫苗的婴儿中普遍存在的亚中和免疫。此外，为了更接近母体抗麻疹免疫干扰的更生理的小动物模型，我们在遗传修饰的、对 MV 易感的小鼠中记录了被动抗 MV 免疫的垂直传递，并在该生理模型中显示出比亲本疫苗株更好的 MVvac2-H2 免疫特征。总之，这些数据支持了增强 MV 血凝素结合可以规避体内中和的观点。这一策略值得进一步探索，作为一种替代的儿科麻疹疫苗。
