Multimerization of Ebola GPΔmucin on protein nanoparticle vaccines has minimal effect on elicitation of neutralizing antibodies.

Multimerization of Ebola GPΔmucin on protein nanoparticle vaccines has minimal effect on elicitation of neutralizing antibodies.
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DOI:
10.3389/fimmu.2022.942897
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发表时间:
2022
影响因子:
7.3
通讯作者:
Kim PS
Kim PS
中科院分区:
医学2区
文献类型:
--
作者:
Powell AE;Xu D;Roth GA;Zhang K;Chiu W;Appel EA;Kim PS

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埃博拉病毒(Ebola virus,EBOV)是丝状病毒科(Filoviridae)病毒的一个成员,也是埃博拉病毒病(Ebola Virus Disease,EVD)的病原体,是一种高致病性病毒,自1976年正式发现以来,已经在中非和西非造成了二十多次疫情。唯一获得FDA许可的埃博拉病毒疫苗rVSV-ZEBOV-GP(Ervebo®)仅在一次剂量后即可有效对抗感染。然而,由于这种疫苗含有复制病毒,它需要超低温储存,这给分配和获取带来了相当大的后勤挑战。更多的候选疫苗可以提供更大的保护,以减轻当前和未来的疫情。在这里,我们设计并表征了两种多聚体蛋白纳米颗粒亚单位疫苗,其展示8或20个拷贝的GPΔ粘蛋白,EBOV表面蛋白GP的截短形式。用GPΔ粘蛋白纳米颗粒对小鼠进行单剂量免疫显示,中和抗体水平大致相当于用非多聚化GPΔ粘蛋白三聚体免疫的小鼠中观察到的水平。这些结果表明,一些蛋白质亚单位抗原在多价支架上展示时不会引起增强的抗体应答,并且可以为下一代稳定的埃博拉病毒候选疫苗的设计提供信息。
Ebola virus (EBOV), a member of the Filoviridae 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.
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