PDF(Pubmed)
Abstract：
Herpes zoster (HZ), also known as shingles, remains a significant global health issue and most commonly seen in elderly individuals with an early exposure history to varicella-zoster virus (VZV). Currently, the licensed vaccine Shingrix, which comprises a recombinant VZV glycoprotein E (gE) formulated with a potent adjuvant AS01B, is the most effective shingles vaccine on the market. However, undesired reactogenicity and increasing global demand causing vaccine shortage, prompting the development of novel shingles vaccines. Here, we developed novel vaccine candidates utilising multiple nanoparticle (NP) platforms to display the recombinant gE antigen, formulated in an MF59-biosimilar adjuvant. In naïve mice, all tested NP vaccines induced higher humoral and cellular immune responses than Shingrix, among which, the gEM candidate induced the highest cellular response. In live attenuated VZV (VZV LAV)-primed mouse and rhesus macaque models, the gEM candidate elicited superior cell-mediated immunity (CMI) over Shingrix. Collectively, we demonstrated that NP technology remains a suitable tool for developing shingles vaccine, and the reported gEM construct is a highly promising candidate in the next-generation shingles vaccine development.
摘要：
带状疱疹（HZ），也被称为带状疱疹，仍然是一个重要的全球健康问题，最常见于有水痘-带状疱疹病毒（VZV）早期接触史的老年人。目前,许可的疫苗Shingrix,它包含与强效佐剂AS01B配制的重组VZV糖蛋白E（gE），是市场上最有效的带状疱疹疫苗。然而,不希望的反应原性和全球需求的增加导致疫苗短缺，促使新型带状疱疹疫苗的开发。这里,我们开发了新的候选疫苗利用多个纳米颗粒（NP）平台来展示重组gE抗原，在MF59生物仿制药佐剂中配制。在幼稚的小鼠中，所有测试的NP疫苗都比Shingrix诱导更高的体液和细胞免疫反应，其中,gEM候选者诱导最高的细胞反应。在活减毒VZV（VZVLAV）引发的小鼠和恒河猴模型中，gEM候选物引起优于Shingrix的细胞介导免疫（CMI）。总的来说，我们证明了NP技术仍然是开发带状疱疹疫苗的合适工具，报道的gEM构建体是下一代带状疱疹疫苗开发中非常有希望的候选者。
