Department of Biochemistry and Stanford ChEM-H, Stanford University, Stanford, CA, United States.
Department of Bioengineering, Stanford University, Stanford, CA, United States.
Front Immunol. 2022 Aug 24;13:942897. doi: 10.3389/fimmu.2022.942897. eCollection 2022.
Ebola virus (EBOV), a member of the family of viruses and a causative agent of Ebola Virus Disease (EVD), is a highly pathogenic virus that has caused over twenty outbreaks in Central and West Africa since its formal discovery in 1976. The only FDA-licensed vaccine against Ebola virus, rVSV-ZEBOV-GP (Ervebo), is efficacious against infection following just one dose. However, since this vaccine contains a replicating virus, it requires ultra-low temperature storage which imparts considerable logistical challenges for distribution and access. Additional vaccine candidates could provide expanded protection to mitigate current and future outbreaks. Here, we designed and characterized two multimeric protein nanoparticle subunit vaccines displaying 8 or 20 copies of GPΔmucin, a truncated form of the EBOV surface protein GP. Single-dose immunization of mice with GPΔmucin nanoparticles revealed that neutralizing antibody levels were roughly equivalent to those observed in mice immunized with non-multimerized GPΔmucin trimers. These results suggest that some protein subunit antigens do not elicit enhanced antibody responses when displayed on multivalent scaffolds and can inform next-generation design of stable Ebola virus vaccine candidates.
埃博拉病毒（EBOV）属于病毒家族的一员，是埃博拉病毒病（EVD）的病原体，是一种高致病性病毒，自 1976 年正式发现以来，已在中非和西非造成二十多次暴发。唯一获得美国食品和药物管理局（FDA）许可的埃博拉病毒疫苗，rVSV-ZEBOV-GP（Ervebo），只需一剂即可有效预防感染。然而，由于这种疫苗含有复制病毒，因此需要超低温储存，这给分发和获取带来了相当大的后勤挑战。其他疫苗候选物可以提供更广泛的保护，以减轻当前和未来的疫情爆发。在这里，我们设计并表征了两种展示 8 或 20 个 GPΔmucin 拷贝的多聚体蛋白纳米颗粒亚单位疫苗，GPΔmucin 是埃博拉病毒表面蛋白 GP 的一种截断形式。单次免疫小鼠的结果表明，纳米颗粒形式的 GPΔmucin 引发的中和抗体水平与用非多聚化的 GPΔmucin 三聚体免疫的小鼠中观察到的水平大致相当。这些结果表明，当某些蛋白亚单位抗原在多价支架上展示时，不会引发增强的抗体反应，这可以为下一代稳定的埃博拉病毒疫苗候选物的设计提供信息。
