Varicella zoster virus (VZV) is a highly contagious human herpes virus responsible for causing chickenpox (varicella) and shingles (herpes zoster). Despite the approval of a highly effective vaccine, Shingrix^®, the global incidence of herpes zoster is increasing and the economic burden to the health care system and society are substantial due to significant loss of productivity and health complications, particularly among elderly and immunocompromised individuals. This is primarily because access to the vaccines remains mostly limited to countries within developed economies, such as USA and Canada. Therefore, similarly effective vaccines against VZV that are more accessible to the rest-of-the-world are necessary. In this study, we aimed to evaluate immunogenicity and memory response induced by three mRNA-LNP-based vaccine candidates targeting VZV’s surface glycoprotein E (gE). C57BL/6 mice were immunized with each candidate vaccine, and humoral and cellular immune responses were assessed. Our results demonstrate that the mRNA-LNP-based vaccine candidates elicited robust and durable humoral responses specific to the gE antigen. Notably, mice vaccinated with the mRNA-LNP vaccines exhibited significantly higher antigen-specific T-cell cytokine production compared to the group receiving Shingrix^®, the current standard of care vaccine. Additionally, mRNA-LNP vaccines induced long-lasting memory response, as evidenced by detection of persistent gE-specific Long-Lived Plasma Cells (LLPCs) and memory T cells four months after final immunization. These findings underscore the potential of our mRNA-LNP-based vaccine candidates in generating potent immune responses against VZV, offering promising prospects for their clinical development as an effective prophylactic vaccine against herpes zoster.

水痘带状疱疹病毒 (VZV) 是一种高度传染性的人类疱疹病毒，可引起水痘（水痘）和带状疱疹（带状疱疹）。尽管高效疫苗 Shingrix ^®已获得批准，但全球带状疱疹发病率仍在增加，由于生产力的显着下降和健康并发症，尤其是老年人和免疫功能低下的个体，给医疗保健系统和社会带来了巨大的经济负担。这主要是因为获得疫苗仍然主要限于发达经济体国家，例如美国和加拿大。因此，需要世界其他地方更容易获得的类似有效的水痘带状疱疹病毒疫苗。在这项研究中，我们旨在评估三种基于 mRNA-LNP 的候选疫苗针对 VZV 表面糖蛋白 E (gE) 诱导的免疫原性和记忆反应。使用每种候选疫苗对 C57BL/6 小鼠进行免疫，并评估体液和细胞免疫反应。我们的结果表明，基于 mRNA-LNP 的候选疫苗引发了针对 gE 抗原的强烈且持久的体液反应。值得注意的是，与接受当前标准护理疫苗Shingrix ^{® 的}小鼠相比，接种 mRNA-LNP 疫苗的小鼠表现出显着更高的抗原特异性 T 细胞细胞因子产生。此外，mRNA-LNP 疫苗诱导了持久的记忆反应，最终免疫四个月后检测到持续的 gE 特异性长寿命浆细胞 (LLPC) 和记忆 T 细胞就证明了这一点。这些发现强调了我们基于 mRNA-LNP 的候选疫苗在产生针对 VZV 的有效免疫反应方面的潜力，为其作为有效的带状疱疹预防性疫苗的临床开发提供了广阔的前景。