Zhan Ying, Deng Yao, Huang Baoying, Song Qianqian, Wang Wen, Yang Yang, Dai Lianpan, Wang Wenling, Yan Jinghua, Gao Gorge F, Tan Wenjie
Key Laboratory of Laboratory Medicine, Ministry of Education, and Zhejiang Provincial Key Laboratory of Medical Genetics, Institute of Medical Virology, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Zhejiang, China; National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
Vaccine. 2019 Apr 3;37(15):2122-2130. doi: 10.1016/j.vaccine.2019.02.063. Epub 2019 Mar 6.
The Zika virus (ZIKV) and poxvirus infection are considered as public health emergencies, necessitating the development of effective vaccines. Here, we report novel recombinant DNA-based and non-replicating vaccinia virus (NTV)-based vaccine candidates that express the precursor membrane-envelope (prME) or envelope (E) glycoproteins of ZIKV. After immunization of BABL/c mice with the vaccines using a homologous protocol (DNA/DNA, NTV/NTV) or heterogeneous (DNA/NTV) protocol, a similar level of anti-E IgG and neutralizing antibodies (microneutralization test) were detected in the mice. However, a significantly higher level of E-specific T cell responses was elicited in mice when a heterogeneous prime-boost protocol was used (DNA/NTV) with either the DNA-based or NTV-based vaccines. Furthermore, neutralizing antibodies and a T cell immune response against the vaccinia virus (VV) were detected in mice that were subjected to the prime-boost protocol (DNA/NTV), whereas those subjected to a homologous NTV/NTV protocol had higher levels of anti-VV IgG and neutralizing antibodies. Lastly, a novel H-2d-restricted CD8 T-cell epitope, VRSYCYEASISDMAS, was identified in the ZIKV E protein. These data demonstrate proof of concept of a bivalent vaccine candidate against ZIKV and orthopoxvirus, and support the use of DNA-prME prime and NTV-E boost protocols to protect against ZIKV and orthopoxvirus infections.
寨卡病毒（ZIKV）和痘病毒感染被视为突发公共卫生事件，因此需要研发有效的疫苗。在此，我们报告了基于重组DNA和非复制型痘苗病毒（NTV）的新型候选疫苗，这些疫苗表达寨卡病毒的前体膜包膜（prME）或包膜（E）糖蛋白。使用同源方案（DNA/DNA、NTV/NTV）或异源方案（DNA/NTV）用这些疫苗免疫BABL/c小鼠后，在小鼠体内检测到相似水平的抗E IgG和中和抗体（微量中和试验）。然而，当使用异源初免-加强方案（DNA/NTV）接种基于DNA或基于NTV的疫苗时，小鼠体内引发的E特异性T细胞反应水平显著更高。此外，在接受初免-加强方案（DNA/NTV）的小鼠体内检测到针对痘苗病毒（VV）的中和抗体和T细胞免疫反应，而接受同源NTV/NTV方案的小鼠体内抗VV IgG和中和抗体水平更高。最后，在寨卡病毒E蛋白中鉴定出一个新的H-2d限制性CD8 T细胞表位VRSYCYEASISDMAS。这些数据证明了一种针对寨卡病毒和正痘病毒的二价候选疫苗的概念验证，并支持使用DNA-prME初免和NTV-E加强方案来预防寨卡病毒和正痘病毒感染。
