National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.
Viruses. 2022 Jun 2;14(6):1214. doi: 10.3390/v14061214.
Herpes zoster (HZ) is caused by the reactivation of latent varicella-zoster virus (VZV) from the sensory ganglia due to aging or immunosuppression. Glycoprotein E (gE) is a widely used vaccine antigen for specific humoral and cellular immune responses. Immediate early protein 63 (IE63) is expressed during latency, suggesting that it is a potential antigen against HZ reactivation. In this study, HZ DNA vaccines encoding gE, IE63, IE63-2A-gE (where 2A is a self-cleaving sequence), or IE63-linker-gE were developed and investigated for immunogenicity in mice. The results showed that each HZ DNA vaccine induced VZV-specific antibody production. The neutralizing antibody titer elicited by IE63-2A-gE was comparable to that elicited by gE or live attenuated HZ vaccine (LAV). IE63-2A-gE-induced gE or IE63-specific INF-γ T cell frequencies in splenocytes were comparable to those of LAV. Furthermore, IE63-2A-gE, gE, or IE63 led to a significant increase in IFN-γ (IE63 stimulation) and IL-2 (gE stimulation) secretion compared to LAV, showing a Th1-biased immune response. Moreover, IE63-2A-gE and gE induced cytotoxic activity of CD8 T cells compared to that of LAV. This study elucidates that the IE63-2A-gE DNA vaccine can induce both humoral and cell-mediated immune responses, which provides a candidate for the development of an HZ vaccine.
带状疱疹(HZ)是由潜伏在感觉神经节中的水痘-带状疱疹病毒(VZV)因衰老或免疫抑制而重新激活引起的。糖蛋白 E(gE)是一种广泛用于特异性体液和细胞免疫反应的疫苗抗原。立即早期蛋白 63(IE63)在潜伏期表达,表明它是针对 HZ 再激活的潜在抗原。在这项研究中,我们开发并研究了编码 gE、IE63、IE63-2A-gE(其中 2A 是自我切割序列)或 IE63-接头-gE 的 HZ DNA 疫苗,以研究其在小鼠中的免疫原性。结果表明,每种 HZ DNA 疫苗都能诱导 VZV 特异性抗体产生。IE63-2A-gE 诱导的中和抗体滴度可与 gE 或减毒活 HZ 疫苗(LAV)诱导的中和抗体滴度相媲美。IE63-2A-gE 诱导的脾细胞中 gE 或 IE63 特异性 INF-γ T 细胞频率与 LAV 相当。此外,与 LAV 相比,IE63-2A-gE、gE 或 IE63 导致 IFN-γ(IE63 刺激)和 IL-2(gE 刺激)分泌显著增加,表现出 Th1 偏向的免疫反应。此外,IE63-2A-gE 和 gE 诱导 CD8 T 细胞的细胞毒性活性高于 LAV。本研究阐明了 IE63-2A-gE DNA 疫苗可以诱导体液和细胞介导的免疫反应,为开发 HZ 疫苗提供了候选疫苗。