Côrtes Nelson, Lira Aline, Silva Jaqueline D Q, Carvalho Evelyn, Prates-Syed Wasim A, Hamaguchi Barbara, Durães-Carvalho Ricardo, Balan Andrea, Câmara Niels O S, Cabral-Marques Otavio, Pardi Norbert, Sabino Ester C, Krieger José E, Cabral-Miranda Gustavo
Department of Infectious Diseases and Tropical Medicine, Laboratory of Medical Investigation 46, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
NPJ Vaccines. 2025 May 27;10(1):107. doi: 10.1038/s41541-025-01163-4.
Still, Zika virus (ZIKV) infection poses a substantial public health risk, especially for pregnant women and their fetuses, as it can result in congenital abnormalities and fetal mortality during pregnancy. Despite significant advances in understanding and combating ZIKV, considerable challenges remain in the fight against this flavivirus. A crucial component of this effort is the development of vaccines, none of which have yet been licensed for human use. Here, we present a comprehensive study of a novel ZIKV vaccine candidate based on virus-like particles (VLPs), designed to provide broad immunological protection against viral infection combined with safety, without the need for additional adjuvants. A self-adjuvanted VLPs-based vaccine displaying the envelope protein domain III (EDIII) of ZIKV was built. The EDIII protein was expressed in E. coli and chemically conjugated to QβVLPs. Immunization of C57BL/6 mice with two doses of the EDIII-QβVLPs vaccine elicited strong EDIII-specific Th1-based immune response. Notably, the vaccine induced neutralizing antibodies and conferred protection in type I IFN receptor-deficient (G129) mice against ZIKV challenge. Furthermore, vaccinated male mice were protected from ZIKV-induced cerebral and testicular damage, critical concerns for ZIKV pathogenesis. These findings suggest that the EDIII-QβVLP vaccine is a promising candidate for preventing ZIKV infection, with potential applications in combatting this and other emerging flaviviruses.
尽管如此，寨卡病毒（ZIKV）感染仍构成重大的公共卫生风险，尤其是对孕妇及其胎儿而言，因为它可导致孕期先天性异常和胎儿死亡。尽管在了解和对抗寨卡病毒方面取得了重大进展，但在抗击这种黄病毒的斗争中仍存在相当大的挑战。这项工作的一个关键组成部分是疫苗的研发，目前尚无一种疫苗获得人类使用许可。在此，我们对一种基于病毒样颗粒（VLPs）的新型寨卡病毒候选疫苗进行了全面研究，该疫苗旨在提供针对病毒感染的广泛免疫保护并兼具安全性，无需额外佐剂。构建了一种展示寨卡病毒包膜蛋白结构域III（EDIII）的基于自佐剂VLPs的疫苗。EDIII蛋白在大肠杆菌中表达并与QβVLPs化学偶联。用两剂EDIII-QβVLPs疫苗免疫C57BL/6小鼠引发了强烈的基于Th1的EDIII特异性免疫反应。值得注意的是，该疫苗诱导产生中和抗体，并在I型干扰素受体缺陷（G129）小鼠中赋予了针对寨卡病毒攻击的保护作用。此外，接种疫苗的雄性小鼠免受寨卡病毒诱导的脑部和睾丸损伤，这是寨卡病毒发病机制中的关键问题。这些发现表明，EDIII-QβVLP疫苗是预防寨卡病毒感染有前景的候选疫苗，在对抗这种及其他新兴黄病毒方面具有潜在应用价值。
