A VLPs based vaccine protects against Zika virus infection and prevents cerebral and testicular damage.

IF 6.9 1区 医学 Q1 IMMUNOLOGY
Nelson Côrtes, Aline Lira, Jaqueline D Q Silva, Evelyn Carvalho, Wasim A Prates-Syed, Barbara Hamaguchi, Ricardo Durães-Carvalho, Andrea Balan, Niels O S Câmara, Otavio Cabral-Marques, Norbert Pardi, Ester C Sabino, José E Krieger, Gustavo Cabral-Miranda
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Abstract

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.

一种基于VLPs的疫苗可以预防寨卡病毒感染,防止大脑和睾丸损伤。
尽管如此,寨卡病毒(ZIKV)感染仍构成重大的公共卫生风险,特别是对孕妇及其胎儿,因为它可导致妊娠期间的先天性异常和胎儿死亡。尽管在了解和抗击寨卡病毒方面取得了重大进展,但在抗击这种黄病毒方面仍存在相当大的挑战。这一努力的一个关键组成部分是开发疫苗,但目前还没有一种疫苗获准供人使用。在这里,我们提出了一项基于病毒样颗粒(vlp)的新型寨卡病毒候选疫苗的综合研究,该疫苗旨在提供广泛的免疫保护,以抵抗病毒感染,同时具有安全性,无需额外的佐剂。构建了具有寨卡病毒包膜蛋白结构域III (EDIII)的vlps自佐剂疫苗。EDIII蛋白在大肠杆菌中表达,并化学偶联到QβVLPs上。两剂EDIII-QβVLPs疫苗免疫C57BL/6小鼠可引起强烈的ediii特异性th1免疫应答。值得注意的是,疫苗诱导了中和抗体,并赋予I型IFN受体缺陷(G129)小鼠抵抗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引起的大脑和睾丸损伤,这是寨卡病毒发病机制的关键问题。这些发现表明,EDIII-QβVLP疫苗是预防寨卡病毒感染的一个有希望的候选疫苗,在对抗寨卡病毒和其他新兴黄病毒方面具有潜在的应用前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
NPJ Vaccines
NPJ Vaccines Immunology and Microbiology-Immunology
CiteScore
11.90
自引率
4.30%
发文量
146
审稿时长
11 weeks
期刊介绍: Online-only and open access, npj Vaccines is dedicated to highlighting the most important scientific advances in vaccine research and development.
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