A new experimental vaccine that could provide protection against multiple varieties of dangerous coronaviruses just passed a major hurdle in its development that may bring it closer to being tested in clinical trials, according to David Martinez, PhD, assistant professor of immunobiology at Yale School of Medicine and a member of the Yale Center for Infection and Immunity. Coronaviruses are behind some of the deadliest outbreaks of the past few decades. These viruses tend to jump from animal hosts to humans. This has occurred at least three times with different coronaviruses during this century. These viruses then produce deadly respiratory illnesses. For these reasons, developing vaccines that can provide broad coverage against lethal coronaviruses is essential. In a study published in Cell Reports, Martinez and colleagues at the Duke Human Vaccine Institute—where Martinez worked before coming to Yale in May 2023—tested a newly developed vaccine intended to protect against three deadly coronaviruses. Two were in the SARS family (for severe acute respiratory syndrome): SARS-CoV-1, which emerged in 2003, and SARS-CoV-2, the virus that led to the COVID-19 pandemic. The other was MERS-CoV, for Middle East respiratory syndrome. Martinez, the study’s first and lead corresponding author, led the research team along with co-corresponding authors Ralph Baric, PhD, of the University of North Carolina; and Barton Haynes, MD, and Kevin Saunders, PhD, of Duke University. The study found that vaccinated mice infected with lethal SARS-CoV-1 and MERS-CoV survived their infections, while unvaccinated mice did not. The vaccine also provided protection against rising SARS-CoV-2 variants, like XBB1.5. This finding could help move the vaccine into phase-1 clinical trials, says Martinez, and—eventually—into people’s arms. Why do we need a universal vaccine? While the year 2020 is inextricably linked with the coronavirus dubbed SARS-CoV-2, that virus is just one of many that can cause illness and death. This massive group of viruses—which can be found in animals all over the world—had shown itself to be a potential danger to people nearly two decades earlier. In 2003, SARS-CoV-1 started infecting people in Asia. Presumed to have jumped to people from bats, it infected around 8,000 people, nearly 800 of whom died—making SARS the first new, highly-infectious disease of the 21st century, according to the World Health Organization. Ten years later, MERS also emerged, this time spilling over into people from camels. Despite their being genetically distinct from one another, the viruses had a few commonalities: each one came from animal hosts, mortality rates were relatively high, and the diseases manifested as respiratory illnesses. “It became very clear that coronaviruses are a public threat to humanity,” says Martinez. And then came “a virus that needs no introduction—SARS-CoV-2.” Martinez started working on a “universal” coronavirus vaccine during his postdoctoral training at the height of the COVID-19 pandemic. After first focusing his research on the development of a vaccine for SARS-CoV-2, he got caught up in the idea of developing a vaccine that could provide broader coverage for other animal-origin coronaviruses. The concept has precedent. Other scientists have tried to develop universal vaccines for HIV and viruses that cause influenza—with mixed success. Martinez and his colleagues searched for an “Achilles heel”—an element that the viruses needed to survive, and that the immune system could be reliably expected to spot. The team chose the RBD receptor, a binding domain found both on MERS and SARS that the viruses need to infect host cells. To make their vaccine, the researchers engineered a scaffold to attach all three versions of the RBD receptor. They then mixed up the vaccine and injected it into their mice, before introducing their subjects to the three deadly viruses. Vaccinated mice all survived. But some of the unvaccinated succumbed to their infections—hinting that the vaccine was key to helping mice fend off the worst of the illness. How would the vaccine protect against infection? Previous studies—including in labs where Martinez has worked—have tested universal vaccines before. But this study is the first to show that a SARS and MERS vaccine can provide protection against three lethal respiratory illnesses in animals, says Martinez. The vaccine “is a triple threat” to the viruses, he says. The vaccine may work because it reduces viral load in the respiratory and nasal passages. One of the reasons that SARS-CoV-2 and other coronaviruses are thought to be so deadly is that the virus accumulates in cells in the lungs. The researchers found that vaccinated mice had lower viral load in their upper airway in the respiratory system than unvaccinated mice—hinting that the vaccine was helping to keep down the viral count and potentially reduce transmission. And the vaccine wasn’t just broadly protective against original variants of SARS-CoV-2. Vaccinated mice also had greater immunity to new COVID variants like XBB1.5, which are being included in the updated versions of the fall COVID booster shots. The universal coronavirus vaccine won’t be available anytime soon. And even if it were, it wouldn’t entirely eliminate the need for boosters, says Martinez, who is continuing his work on universal vaccines at Yale. But if it passes clinical trials, it might lengthen the time needed between boosters, he says, as newer variants would have less of an edge than they do now. The vaccine may be good news for more just than tackling coronaviruses. If a universal coronavirus vaccine is approved, it could open the door for developing other universal vaccines to tackle tricky or deadly illnesses, including influenza, Martinez says.