Abstract
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.
Highlights
Emerging zoonotic infectious diseases present a significant global health burden
To assess the immune response induced by the Zika virus (ZIKV) pre-membrane and envelope (prM–E) Messenger RNA (mRNA)-lipid nanoparticles (LNPs) vaccine candidate, we vaccinated 8–12 weeks old BALB/c mice twice
The geometric mean titer (GMT) of the group immunized twice with 5 μg of ZIKV prM–E mRNA-LNP vaccine did not increase after challenge (p = 0.7370), while high PRNT50 titers were detected after challenge on day 44 for surviving mice in the remaining vaccine groups (p < 0.0001)
Summary
Emerging zoonotic infectious diseases present a significant global health burden. While the first case of ZIKV infection in humans was detected in Nigeria in 1952 [1], this arbovirus, transmitted from Aedes spp. mosquitoes, was unremarkable for decades until outbreaks occurred between 2007 to 2017 on Yap Island [2], French Polynesia [3], and the Americas [4]. The global interest was primarily due to the detrimental fetal outcomes in pregnant women infected with ZIKV in Brazil and other countries around the world [6]. Global interest in Zika has led to a variety of vaccine candidates, to date, there is no licensed vaccine for the disease. Vaccine platforms targeting the viral envelope protein (E), responsible for mediating cell fusion, and the pre-membrane protein (prM) induce high levels of nAbs. Potential vaccine platforms against Zika need to be safely administered to pregnant women, the most vulnerable population at risk for ZIKV infection. Since pregnant women have strated in the global pandemic of COVID-19, mRNA vaccine technology is fective means to stimulate protective immune responses. We ai tigate a Zika vaccine candidate using LNP encapsulated mRNA technolog clinical development.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
