Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Institute of Medical Virology, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China; NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
Tianjin International Joint Academy of Biomedicine, Tianjin, China.
Infect Genet Evol. 2020 Nov;85:104521. doi: 10.1016/j.meegid.2020.104521. Epub 2020 Sep 1.
The recent pandemic of Zika virus (ZIKV) infections highlight the urgent need for the development of a safe and efficacious ZIKV vaccine. We previously demonstrated that robust humoral and cellular immunity was elicited in BALB/c mice by ZIKV DNA vaccine encoding the precursor membrane (prM) and envelope (E) proteins while the protective efficacies were not evaluated against ZIKV challenge. To further explore the protective immunity elicited by various targets of ZIKV, we constructed a novel DNA-based vaccine expressing nonstructural protein 1 (NS1), named as VRC-NS1, and evaluated and compared immune responses and protective efficacies of three ZIKV DNA vaccine candidates (VRC-prME, VRC-NS1, and VRC-prME+VRC-NS1) using an A129 (Ifnar) murine challenge model. The results showed that each of DNA vaccine candidates induced robust antigen-specific humoral immunity and conferred protection against ZIKV-SMGC-1 with two doses (20 μg per dose) of homologous intramuscularly (i.m.) immunizations via in vivo electroporation. All DNA vaccine candidates induced significant protection against infection-associated weight loss in addition to preventing viral replication in blood, brain and spleen tissue following in vivo viral challenge. Notably, NS1-based DNA vaccination alone was capable of conferring mouse protective immunity to reduce viremia and viral burden in tissues against ZIKV challenge, even though it did not induce neutralizing antibodies. These data demonstrated that VRC-NS1 and VRC-prME are highly promising vaccine candidates for ZIKV control. Furthermore, our results highlight an alternative strategy (DNA vaccine based on non-neutralizing antigen NS1) for designing novel flaviviral vaccines (including for ZIKV) and provide a foundation for the development of a safe and effective NS1-based vaccine against ZIKV infection.
最近的 Zika 病毒（ZIKV）感染疫情凸显了开发安全有效的 ZIKV 疫苗的迫切需要。我们之前的研究表明，ZIKV DNA 疫苗编码前膜（prM）和包膜（E）蛋白可在 BALB/c 小鼠中引发强大的体液和细胞免疫，但未评估其对 ZIKV 攻击的保护效力。为了进一步探索 ZIKV 各种靶标引发的保护免疫，我们构建了一种表达非结构蛋白 1（NS1）的新型 DNA 疫苗，命名为 VRC-NS1，并使用 A129（Ifnar）鼠挑战模型评估和比较了三种 ZIKV DNA 疫苗候选物（VRC-prME、VRC-NS1 和 VRC-prME+VRC-NS1）的免疫反应和保护效力。结果表明，每种 DNA 疫苗候选物均诱导了强大的抗原特异性体液免疫，并通过体内电穿孔进行两次同源肌内（i.m.）免疫（每次 20μg），对 ZIKV-SMGC-1 提供了保护。所有 DNA 疫苗候选物均显著预防了感染相关的体重减轻，并在体内病毒攻击后阻止了血液、大脑和脾脏组织中的病毒复制。值得注意的是，单独的 NS1 基 DNA 疫苗接种能够赋予小鼠保护免疫，以降低针对 ZIKV 攻击的病毒血症和组织中的病毒载量，尽管它没有诱导中和抗体。这些数据表明，VRC-NS1 和 VRC-prME 是控制 ZIKV 的极有前途的疫苗候选物。此外，我们的结果强调了针对新型黄病毒疫苗（包括 ZIKV）设计的替代策略（基于非中和抗原 NS1 的 DNA 疫苗），并为开发针对 ZIKV 感染的安全有效的 NS1 基疫苗提供了基础。
