Medina-Magües Lex G, Gergen Janina, Jasny Edith, Petsch Benjamin, Lopera-Madrid Jaime, Medina-Magües Emily S, Salas-Quinchucua Cristhian, Osorio Jorge E
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.
CureVac AG, Friedrich-Miescher-Straße 15, 72076 Tübingen, Germany.
Vaccines (Basel). 2021 Dec 10;9(12):1464. doi: 10.3390/vaccines9121464.
Zika virus (ZIKV), a mosquito-borne flavivirus, has recently triggered global concern due to severe health complications. In 2015, a large ZIKV outbreak occurred in the Americas and established a link between ZIKV and microcephaly in newborn babies, spontaneous abortion, persistent viremia, and Guillain-Barré syndrome. While antivirals are being developed and prevention strategies focus on vector control, a safe and effective Zika vaccine remains unavailable. Messenger RNA (mRNA) vaccine technology has arisen as a flexible, simplified, and fast vaccine production platform. Here, we report on an mRNA vaccine candidate that encodes the pre-membrane and envelope (prM-E) glycoproteins of ZIKV strain Brazil SPH2015 and is encapsulated in lipid nanoparticles (LNPs). Our ZIKV prM-E mRNA-LNP vaccine candidate induced antibody responses that protected in AG129 mice deficient in interferon (IFN) alpha/beta/gamma (IFN-α/β/γ) receptors. Notably, a single administration of ZIKV prM-E mRNA-LNP protected against a lethal dose of ZIKV, while a two-dose strategy induced strong protective immunity. E-specific double-positive IFN-γ and TNF-α T-cells were induced in BALB/c mice after immunizations with a two-dose strategy. With the success of mRNA vaccine technology in facing the coronavirus (COVID-19) pandemic, our data support the development of prM-E RNActive as a promising mRNA vaccine against Zika to counter future epidemics.
寨卡病毒（ZIKV）是一种由蚊子传播的黄病毒，最近因其引发的严重健康并发症而引起全球关注。2015年，美洲爆发了大规模寨卡病毒疫情，并发现寨卡病毒与新生儿小头畸形、自然流产、持续性病毒血症和格林-巴利综合征之间存在关联。虽然抗病毒药物正在研发中，预防策略主要集中在病媒控制上，但安全有效的寨卡疫苗仍然无法获得。信使核糖核酸（mRNA）疫苗技术已成为一种灵活、简化且快速的疫苗生产平台。在此，我们报告一种候选mRNA疫苗，它编码寨卡病毒巴西SPH2015株的前膜和包膜（prM-E）糖蛋白，并封装在脂质纳米颗粒（LNPs）中。我们的寨卡病毒prM-E mRNA-LNP候选疫苗诱导了抗体反应，在缺乏α/β/γ干扰素（IFN-α/β/γ）受体的AG129小鼠中起到了保护作用。值得注意的是，单次注射寨卡病毒prM-E mRNA-LNP可抵御致死剂量的寨卡病毒，而两剂接种策略则诱导了强大的保护性免疫。采用两剂接种策略免疫后，BALB/c小鼠体内诱导产生了E特异性双阳性IFN-γ和TNF-α T细胞。鉴于mRNA疫苗技术在应对冠状病毒（COVID-19）大流行中取得成功，我们的数据支持将prM-E RNActive开发为一种有前景的抗寨卡mRNA疫苗，以应对未来的疫情。
