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Learning from COVID, researchers prep universal vaccine for next coronavirus outbreak

It's too late to save the world from COVID-19, but a universal vaccine could mean future coronaviruses won't become pandemics

Imagine if a single vaccine not only quashed the current COVID-19 pandemic but promised to combat future coronavirus outbreaks as well.

“We've lost millions of lives, and economies have taken huge hits because we didn't have a universal coronavirus vaccine sitting on the shelf,” said Dr. Nelson Michael, director of the Center for Infectious Disease Research at the Walter Reed Army Institute of Research.

In January 2020, Nelson’s lab was developing vaccination against the deadly respiratory virus MERS but quickly pivoted to study SARS-CoV-2, the virus that causes the deadly respiratory disease COVID-19.

To date, COVID has killed 5.3 million people worldwide and continues to infect hundreds of thousands each day.

In November, the Walter Reed vaccine — which would provide immunity against several different coronaviruses — completed phase 1 human trials, marking an important step forward. Unlike the mRNA vaccines developed at warp speed to combat COVID-19, universal coronavirus vaccines remain several years away from distribution.

Still, lessons from COVID-19 indicate now is the perfect time to develop future treatments.

In addition to causing the SARS epidemic of 2002 and MERS in 2012, coronaviruses drive the human cold and other common animal diseases. Besides being abundant and spreading rapidly, coronaviruses have proven difficult to eradicate because they change very quickly.

“Coronaviruses undergo rapid viral evolution, so we're always chasing the new viral variants that emerge,” said Deborah Fuller, a microbiology professor at the University of Washington School of Medicine. “In the gap between the time that the virus first emerges and when we update our vaccines, there can be significant mortality and morbidity in the population.”

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She added: “Of course, the biggest concern in the future is that we may have at some point another zoonotic transmission of a coronavirus, as we've seen in the past."

Both SARS and SARS-CoV-2 are sarbecoviruses, shaped like the ball on a medieval flange with dozens of spike proteins sticking out all over. When the spike protein latches onto a host cell, the virus fills the host with genetic material directing it to make more viruses.

Current Pfizer and Moderna COVID-19 vaccines use genetic material known as mRNA to instruct human cells to make spike proteins; this triggers the immune system to build defenses to protect the body from COVID-19 viruses in the wild.

These vaccines remain effective as long as they adequately prepare the immune system for whatever spike proteins it will face on a given coronavirus or variant. Likewise, a universal coronavirus vaccine could prepare the body to face numerous variations of spike proteins and other compounds as well.

Leading research from the University of North Carolina and Duke University demonstrate attaching a variety of spike shapes to nanoparticles, creating a chimeric vaccine to enable the immune system to recognize many possible spike protein shapes at once.

Importantly, the spike protein is highly conserved across coronaviruses, meaning the structure is something the virus needs to function and isn’t likely to lose.

“If you can target the conserved sites within the spike protein, then you can limit how the virus is able to infect cells,” said Dr. Kevin Saunders, director of research for the Duke Human Vaccine Institute. “But if you look at the coronavirus genome as a whole and all the proteins that make the spike protein, that is what changes most often because your immune response is directed at it.”

Researchers quickly identified spike protein mutations that helped the Delta variant become the dominant global strain of COVID-19 within six months of its discovery. Likewise, the Omicron variant, which emerged in November, exhibits more spike mutations than previously observed.

Although the spike protein has become an Achilles' heel for many, other researchers worry this approach is too narrow and evadable.

“Everyone’s looking for a magic bullet,” said Dr. Matthew Memoli, director of the Laboratory of Infectious Diseases Clinical Studies Unit at the National Institute of Allergy and Infectious Diseases.

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“The reality is that when we focus on a single antigen, we are giving the virus plenty of room to change and evade that immunity,” Memoli said. “What I believe we need to do is take some of these strategies that people are coming up with and incorporate them into a broader strategy, targeting as many if not all the antigens present in a particular virus.”

In addition to developing a universal vaccine against coronaviruses, researchers say it must be universally distributed.

“Having adequate vaccine distribution globally is not really an altruistic undertaking because stopping the spread of COVID-19 around the world is a way of protecting ourselves here,” argued Steven Zeichner, professor of pediatrics and microbiology at the University of Virginia. “If you have some even nastier variant come up in a poor country with inadequate vaccine coverage, it will be here sooner or later.”

At the University of Virginia, Zeichner’s lab targeted the coronavirus fusion peptide, a key compound used by the virus to grab onto host cells.

“That fusion peptide cannot be changed and is something the virus absolutely has to have as it exists now,” Zeichner explained. The compound can also be grown with genetically modified bacteria, a method currently used to produce whooping cough and cholera vaccines worldwide.

Zeichner envisions the fusion peptide vaccine being made for $1 per dose and distributed far more widely than current temperature-sensitive mRNA vaccines.

Even with early success and peer-reviewed proofs of concept, most researchers caution it will be years before a broad-coronavirus vaccine is readily available. Though this treatment won’t come in time to save the world from COVID-19, with luck it will be ready to prevent the next pandemic.

If, of course, the public is ready for it.

“The biggest problem that we have is that we don't put enough money into implementation research,” said Dr. Nelson Michael, of the Walter Reed Army Institute of Research. “We still have a very significant part of our own population in the United States that could walk to a pharmacy, or drive to one in a few minutes, but won't take the [COVID-19] vaccine because we failed to figure out how to get that important tool implemented.”

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NIAID-RML

This transmission electron microscope image shows SARS-CoV-2, the virus that causes COVID-19, isolated from a patient in the U.S. Virus particles are shown emerging from the surface of cells cultured in the lab. The spikes on the outer edge of the virus particles give coronaviruses their name, crown-like.