Coleman Christopher M, Liu Ye V, Mu Haiyan, Taylor Justin K, Massare Michael, Flyer David C, Smith Gale E, Frieman Matthew B
University of Maryland School of Medicine 685 West Baltimore St Baltimore, MD 21201.
Novavax, Inc. 22 Firstfield Rd Gaithersburg, MD 20852.
Vaccine. 2014 May 30;32(26):3169-3174. doi: 10.1016/j.vaccine.2014.04.016. Epub 2014 Apr 13.
Development of vaccination strategies for emerging pathogens are particularly challenging because of the sudden nature of their emergence and the long process needed for traditional vaccine development. Therefore, there is a need for development of a rapid method of vaccine development that can respond to emerging pathogens in a short time frame. The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in late 2012 demonstrate the importance of coronaviruses as emerging pathogens. The spike glycoproteins of coronaviruses reside on the surface of the virion and are responsible for virus entry. The spike glycoprotein is the major immunodominant antigen of coronaviruses and has proven to be an excellent target for vaccine designs that seek to block coronavirus entry and promote antibody targeting of infected cells. Vaccination strategies for coronaviruses have involved live attenuated virus, recombinant viruses, non-replicative virus-like particles expressing coronavirus proteins or DNA plasmids expressing coronavirus genes. None of these strategies has progressed to an approved human coronavirus vaccine in the ten years since SARS-CoV emerged. Here we describe a novel method for generating MERS-CoV and SARS-CoV full-length spike nanoparticles, which in combination with adjuvants are able to produce high titer antibodies in mice.
针对新出现病原体的疫苗接种策略的开发尤其具有挑战性,因为它们出现得很突然,且传统疫苗开发需要很长时间。因此,需要开发一种快速的疫苗开发方法,以便能在短时间内应对新出现的病原体。2003年严重急性呼吸综合征冠状病毒(SARS-CoV)的出现以及2012年末中东呼吸综合征冠状病毒(MERS-CoV)的出现,证明了冠状病毒作为新出现病原体的重要性。冠状病毒的刺突糖蛋白位于病毒粒子表面,负责病毒进入。刺突糖蛋白是冠状病毒的主要免疫显性抗原,已被证明是疫苗设计的一个极佳靶点,这类疫苗旨在阻止冠状病毒进入并促进抗体靶向感染细胞。针对冠状病毒的疫苗接种策略包括减毒活病毒、重组病毒、表达冠状病毒蛋白的非复制性病毒样颗粒或表达冠状病毒基因的DNA质粒。自SARS-CoV出现以来的十年里,这些策略均未发展成为获批的人类冠状病毒疫苗。在此,我们描述了一种生成MERS-CoV和SARS-CoV全长刺突纳米颗粒的新方法,该方法与佐剂结合能够在小鼠体内产生高滴度抗体。