Experimental mRNA vaccine may protect against multiple Ebola viruses

A new mRNA vaccine has been developed that may provide long-term protection against the deadliest viruses in the Ebola family – including the Bundibugyo strain currently spreading in two African countries.

Over 600 people are thought to have been infected with Bundibugyo virus in the Democratic Republic of the Congo and there have been two confirmed cases in Uganda, leading the World Health Organization to declare the outbreak a public health emergency of international concern.

Bundibugyo virus is a member of a group of pathogens known as orthoebolaviruses, which also includes the most common form of Ebola – the Zaire virus – and Sudan virus. All three can cause severe disease in humans.

Until now, Bundibugyo outbreaks have been rare compared with those of the Zaire strain, which infected over 28,000 people between 2014 and 2016. There are two approved vaccines for the Zaire virus, but none for the Bundibugyo or Sudan viruses.

Now, Yanfeng Yao at the Wuhan Institute of Virology in China and his colleagues say they have developed a vaccine that works in mice to protect against all three viruses.

“The development of a broad-spectrum vaccine has the potential to efficiently mitigate outbreaks caused by multiple orthoebolaviruses,” they write in a new paper presenting their research.

The challenge for scientists trying to produce a vaccine effective for all three of these Ebola-family viruses is that they each carry different compounds, called glycoproteins, that are essential for infection. However, they all share the same nucleoproteins that package the virus’s genetic material.

To build their new vaccine, Yao and his team combined the mRNA encoding the glycoproteins of each virus – as well as the shared nucleoprotein – inside a single lipid nanoparticle, which is a sphere of fat molecules that protects the mRNA vaccine until it can reach the body’s cells.

Mice were administered the vaccine and monitored to see if their immune system responded, before being exposed to all three viruses. All immunised animals gained complete protection against infection by the Zaire and Sudan viruses and were conferred “strong” protection from Bundibugyo. Hamsters exposed to Sudan virus were also afforded complete protection by the vaccine.

The researchers say the trials show they have developed a broad-spectrum mRNA vaccine that effective defends against the Zaire, Sudan and Bundibugyo vaccines. But they also caution that the vaccine has only been tested on rodents so far, and plenty more work is needed to show it is safe and effective in humans.

Robert Cross at the University of Texas Medical Branch says he is “glad to see more creative next-generation [Ebola] vaccines being explored”.

However, he warns that testing in non-human primates is the gold standard for predicting efficacy in humans, and it will be difficult to get approval for a vaccine targeting multiple pathogens.

“It’s hard enough to get a vaccine approved for a specific virus. Getting to license with a multivalent vaccine has an arguably more complex path to approval,” says Cross.

Adrian Esterman at Adelaide University in Australia says it is a promising preclinical study, but a limitation is that the findings only apply to rodents.

“It is probably too early to give a firm timeframe for clinical use, but moving from this stage to human trials would usually take several years because further animal work – for example in primates – manufacturing development and safety testing are still needed,” he says.