One-stop shot – the scientists developing a ‘universal’ coronavirus vaccine

One-stop shot – the scientists developing a ‘universal’ coronavirus vaccine

Vaccine for the World

Researchers are hopeful that a variant-proof vaccine is within their grasp - to protect us from this pandemic and to prevent the next one

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Sarah Wild
4 March 2022
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Imagine if a single vaccine could protect us against not only new variants of the current coronavirus, Covid-19, but also against coronaviruses that do not yet exist.

Buoyed by the creation of several working vaccines against Covid in under a year, scientists now have a “universal vaccine” in their sights.

In January, senior US scientists including chief medical advisor Anthony Fauci, called for more research into a universal coronavirus vaccine. The Coalition for Epidemic Preparedness Innovations (CEPI), a global organisation created to develop vaccines against future pandemics, has earmarked $200 million for a vaccine to protect against variants of the current virus, SARS-CoV-2, and any coronaviruses that may plausibly emerge in the future.

Meanwhile, the National Institutes of Health in the United States has awarded $36 million to “pan-coronavirus” vaccine research.

Since 2000, a novel lethal coronavirus has emerged every decade: Severe Acute Respiratory Syndrome (SARS-CoV-1) in 2003, Middle East Respiratory Syndrome (MERS) in 2012, and SARS-CoV-2 in 2019.

While authorities are racing to keep up with SARS-CoV-2 variants, scientists say it is a matter of time before a new virus emerges, possibly jumping from animals to humans.

But researchers are hopeful that a universal coronavirus vaccine is within their grasp.

Some efforts focus on SARS-CoV-2 and aim to create a “variant-proof” vaccine against current and future variants. Others aim to vaccinate against SARS-like viruses, which include known and potential future coronaviruses.

Third, some researchers are tackling a subgroup of coronaviruses, known as “Beta” (which is confusingly not the same as the SARS-CoV-2 variant called Beta). The Beta group includes SARS-like viruses, MERS, two of the cold-causing viruses, and a number of bat-related coronaviruses.

“If we could make a vaccine that protects against Beta coronaviruses that would be fantastic,” says Jason McLellan, a molecular bioscientist at the University of Texas at Austin, whose group is focusing on a Beta coronavirus vaccine. “It is a high bar, though.”

The idea of a universal vaccine against a virus is not new. For more than a decade, scientists have been trying to find a vaccine against influenza. Currently, the annual flu vaccine contains three or four virus strains, but there are many more that do not get included and influenza viruses evolve quickly and there are so many strains that some years the vaccine is more effective than others.

Despite hundreds of millions of dollars in funding and years of research, there is still no universal flu vaccine. However, given the colossal social and economic fallout of Covid-19, the impetus to create a coronavirus vaccine is even greater. Also in the potential vaccine’s favour is the fact that coronaviruses are less complex than influenza and are more constrained in the way that they can evolve.

Fusion Medical Animation/Unsplash

They find infected cells and get rid of them, and so take out the virus factories

There are a number of ways to approach creating immunity through vaccines, but they tend to focus on either antibodies or on T-cells. “Antibodies are those little torpedoes that your body creates to block the virus from getting into a cell,” explains Paul Thomas, an immunologist at St. Jude Children’s Research Hospital in Tennessee in the United States.

On the other hand, CD8 T-cells, also known as “killer T-cells”, target infected cells. “They find infected cells and get rid of them, and so take out the ‘virus factories’. That is what ultimately ends your infection.”

Antibody-focused vaccines want to provoke an antibody response that will identify coronaviruses and neutralise the virus before it infects people’s cells.

In her lab at the California Institute of Technology, biochemist Pamela Björkman is looking to generate antibody responses to SARS-like coronaviruses with nanoparticles. These nanoparticles are covered with a specific part of various SARS-like viruses, called the receptor binding domain. This part, located on the spike protein, is what latches onto human cells, and is what often mutates to avoid the immune system.

The scientists stuck eight receptor binding domains from different SARS-like viruses, including SARS-CoV-2, to the nanoparticles. Although the domains come from different viruses, they have many sections in common – and this is what the scientists want antibodies to recognise.

The team has shown that these laden nanoparticles can induce broad antibody responses in animals. And the hope is these antibodies would fight off coronaviruses that we have not seen yet but share similarities with SARS-like viruses.

McLellan’s coronavirus vaccine research is also looking to exploit commonalities between different coronaviruses. His target, though, is not the receptor binding domain, but the part of the spike protein that will fuse the virus and cell together. He and colleagues have designed and produced antigens, which they are currently testing in mice. Depending on how the mice react, they will tweak the antigen until they have a possible vaccine candidate. Optimistically, they are looking at a timeline of three to five years, he says.

Paul Thomas’ team in Tennessee, on the other hand, is working on killer T-cells, which recognise different parts of the virus in infected cells.

Thomas and collaborators are tracking large numbers of people who have been infected with SARS-CoV-2 over the last two years, identifying the little pieces of the virus that the T-cells see, and linking that to Covid outcomes.

What will the efficacy be like against coronaviruses that maybe haven’t even emerged yet?

A lot of the current research into a coronavirus vaccine is only possible because of the significant leaps in molecular techniques over the last two years, leaving researchers in uncharted regulatory territory.

“There’s no regulatory pathway to licence such a vaccine at the moment,” says CEPI’s head of vaccine research and development, Melanie Saville. As such, there are no guidelines on what safety data is required, and how researchers would demonstrate efficacy.

And another question mark over a universal coronavirus vaccine is how to test them. “What will the efficacy be like against coronaviruses that maybe haven’t even emerged yet?”

However, if researchers succeed in finding coronavirus vaccines –whether for variants of SARS-CoV-2 or more broadly for groups of coronavirus – it could save humanity from the next pandemic.

“The idea is that we can have one or more of these (candidates) on standby,” McLellan says. Then, at the first warning that a new coronavirus may be emerging, “we could rapidly test each of these and then start producing the vaccines – or there are already 100 million stockpiled.”

At the very least, this research could be adapted to other viruses, such as influenza or HIV. “It’s like going to the moon,” McLellan says. “It will spin off lots of cool technology that can hopefully be applied to other pathogens as well.”

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