Ebola Virus mRNA Vaccines
Ebola virus disease (EVD), caused by the Ebola virus (EBOV), is a life-threatening neglected tropical disease (with mortality rates up to 90%) in humans and other animal reservoirs. This disease has recently risen to prominence with the unprecedented EBOV epidemic in West Africa, causing more than 11000 deaths. At present, rVSV-ZEBOV (tradename “Ervebo”), a recombinant vesicular stomatitis virus-based vaccine (VSV-EBOV), has been approved by the U.S. Food and Drug Administration, providing a critical weapon against EBOV. However, based on viral vectors, there are several problems, including adverse effects, complex manufacturing requirements, and so on. To face the potentiality of unpredictable and uncontrolled outbreaks, there is an urgent demand for safe, efficient, and rapidly scalable vaccines. Recently, the advance of mRNA-based technologies has accelerated the development of vaccines against infectious diseases, including EVD. Here, we give an overview of mRNA vaccines against EBOV.
A life-threatening neglected tropical disease
Ebola virus disease (EVD) is a rare and fatal disease mainly located in sub-Saharan Africa. As one of the most deadly infectious diseases, EVD is believed to be a zoonosis transmitted by bats, chimpanzees, monkeys, and other animal reservoirs. Humans can be infected with the Ebola virus (EBOV) through close contact with infected animals, then the virus spreads from person to person. There are a series of symptoms developed after EVD infection, including fever, fatigue, muscle pain, diarrhea, rash, multi-system organ failure, and usually leading to death. Over the past decade, there have been two outbreaks of EVD, including the first and largest outbreak between 2014 and 2016 in West Africa and the second ongoing outbreak in the Democratic Republic of the Congo (DRC) and Guinea from 2018. However, the development of EBOV vaccines has been hindered by two common problems. Since the outbreaks of EVD have been sporadic, there have been few opportunities for rigorous clinical testing of experimental vaccines. And the high cost of vaccine development is another reason.
Application of mRNA technology to EBOV
The size and frequency of Ebola outbreaks have been dramatically increased in recent years due to the continuous human expansion into ecologies and the ubiquitous human migration. To develop safer, rapidly designed, and less-reactogenic EBOV vaccine, the mRNA-based platform is an excellent option. Compared to VSV-based vaccines (the current EBOV vaccine), mRNA-based technology as a non-integrating vaccine platform is safer, more rapid and scalable. In recent years, both non-replicative and self-replicating mRNA vaccines have been developed against EBOV. Among them, a dendrimer nanoparticle (NP)-based mRNA replicon encoding EBOV glycoprotein (GP) has been developed and evaluated in preclinical studies. The results showed that intramuscular administration of EBOV GP vaccine (a single or two immunizations) induced protective immune responses in mice. Besides, a nucleoside-modified mRNA-LNP vaccine has been evaluated in guinea pigs. Intramuscular administration of EBOV GP mRNA-LNP vaccine elicit high titers of GP-specific neutralizing antibodies. Importantly, the vaccinated animals all survived with the lethal virus challenge. These preclinical results support the entry of EBOV mRNA vaccines into clinical trials as promising vaccine candidates.
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