Fuentes Sandra, Ravichandran Supriya, Coyle Elizabeth M, Klenow Laura, Khurana Surender
Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
iScience. 2020 Mar 27;23(3):100920. doi: 10.1016/j.isci.2020.100920. Epub 2020 Feb 19.
Limited knowledge exists on the quality of polyclonal antibody response generated following Ebola virus (EBOV) infection compared with vaccination. Polyclonal antibody repertoire in plasma following EBOV infection in survivors was compared with ChAd3-MVA prime-boost human vaccination. Higher antibody binding and affinity to GP was observed in survivors compared with vaccinated plasma that correlated with EBOV neutralization. Surprisingly, a predominant IgM response was generated after prime-boost vaccination, whereas survivors demonstrated IgG-dominant antibody response. EBOV infection induced more diverse antibody epitope repertoire compared with vaccination. A strong binding to antigenic sites in the fusion peptide and another in the highly conserved GP2-HR2 domain was preferentially recognized by EBOV survivors than vaccinated individuals that correlated strongly with EBOV neutralization titers. These findings will help development and evaluation of effective Ebola countermeasures including therapeutics and vaccines.
与接种疫苗相比，关于埃博拉病毒（EBOV）感染后产生的多克隆抗体反应质量的知识有限。将幸存者感染EBOV后血浆中的多克隆抗体库与ChAd3-MVA初免-加强人类疫苗接种后的情况进行了比较。与接种疫苗的血浆相比，在幸存者中观察到更高的抗体与GP的结合及亲和力，这与EBOV中和相关。令人惊讶的是，初免-加强疫苗接种后产生了主要的IgM反应，而幸存者表现出以IgG为主的抗体反应。与接种疫苗相比，EBOV感染诱导了更多样化的抗体表位库。EBOV幸存者比接种疫苗的个体更优先识别与融合肽中的抗原位点以及高度保守的GP2-HR2结构域中的另一个抗原位点的强结合，这与EBOV中和滴度密切相关。这些发现将有助于开发和评估包括治疗方法和疫苗在内的有效的埃博拉应对措施。
