The scientific quest for a universal coronavirus vaccine received a boost Wednesday, as three top federal researchers, including Dr. Anthony Fauci, outlined a path to develop new vaccines that could tackle a variety of ailments including Covid-19, some common colds and future viruses.
Writing in the New England Journal of Medicine, Fauci and two colleagues said the virus that causes Covid-19 is unlikely to be eliminated, and current vaccines are too limited to prevent the emergence of new variants. Other coronaviruses are also likely to spill over from animals to become future pandemic threats, they wrote.
To overcome these problems, the authors argue the research world should “fully commit” to developing a “second-generation” of coronavirus vaccines that would provide broad protection across the genetic spectrum of coronaviruses. They suggest forming an international effort to collect animal coronavirus samples worldwide and developing ethical challenge trials for coronaviruses, among other measures.
During the past two decades, the world has seen four deadly coronavirus outbreaks, including two bouts with SARS in the early 2000s, the emergence of MERS in 2012 and now Covid-19, which has killed more than 800,000 Americans.
The commentary offers no quick fix for the pandemic. But Fauci’s endorsement of the universal vaccine approach could serve as a clarion call and blueprint for scientists.
“It’s good as a roadmap,” Pablo Penaloza-MacMaster, a viral immunologist and assistant professor at Northwestern University, said of the paper. “It creates some scientific clarity: What are the specific hurdles for developing universal vaccines?”
Researchers have been chasing so-called universal vaccines for years. Scientists have been testing universal vaccines against influenza for more than a decade, with the goal of providing long-lasting protection that wouldn’t require a yearly flu shot. The first human clinical trial for a universal influenza vaccine began in 2019; a vaccine has yet to reach the market.
The new paper isn’t the first instance in which Fauci has mentioned the importance of a universal vaccine for coronaviruses. But the emergence of highly mutated variants like omicron, which could compromise the level of protection offered by available vaccines, has made the chase for a long-term solution more urgent.
The National Institutes of Health in September announced that it had invested more than $36 million in university efforts toward vaccines that could neutralize many coronaviruses.
“We are certainly making it a high priority,” Fauci told The Washington Post this month. “There are fundamental scientific challenges before you can actually make a full-court press on this. It isn’t as if you have a clear pathway into a product and all you have to do is dump more resources into it.”
To develop a universal vaccine, Fauci, Dr. David Morens and Dr. Jeffery Taubenberger, suggest creating a collaborative international effort to collect samples from animals like bats, palm civets and raccoon dogs, which are frequent hosts, or reservoirs, of coronaviruses that could jump to people.
Sequencing the genomes of such viruses could help researchers identify new threats and discover commonalities between coronaviruses that a new vaccine could then target.
The authors -- who are all high-ranking doctors at the National Institute of Allergy and Infectious Diseases (NIAID) -- also suggest more research into other coronaviruses suspected of causing pandemics long ago, before they became permanent fixtures that cause common colds.
Scientists should also find cellular targets common to many coronaviruses that vaccines could help attack, identify vaccine candidates that spur long-term immune responses and figure out how best to test in animals, the paper says.
Testing universal vaccines in human challenge studies will be important, too, the authors argue. That type of research could accelerate vaccine development, but it’s ethically complicated because it involves intentionally infecting people to test a vaccine.
While many scientists view human challenge studies for Covid-19 as unethical because it is so severe, it might be possible to design responsible studies for viruses that cause colds or another proxy. Researchers have conducted challenge studies in influenza trials.
Developing a universal coronavirus vaccine “seems to be feasible,” said Penaloza-MacMaster. His own research has indicated that existing vaccines could protect mice against coronaviruses that weren’t the original target.
But achieving a universal coronavirus vaccine could take years, Penaloza-MacMaster said. It could also require more than one vaccine to cover different families of coronavirus, he said, because the mice received more protection against viruses that were more genetically similar.
The paper’s proposal is ambitious.
Collecting viral samples from bat caves, animal markets and people who interact with these creatures “requires a lot of work” and needs strong biosafety precautions to ensure the virus can’t accidentally jump to humans.
“You have people going into the caves where bats are. You don’t want spillovers,” Penaloza-MacMaster said.
At least a half-dozen research groups are already evaluating universal vaccine candidates and searching for the best parts of coronaviruses to target, he said.
The current coronavirus vaccines made by Moderna, Pfizer and Johnson & Johnson take aim at the spike protein, which Penaloza-MacMaster calls the “Achille's heel” of the virus, though it’s also a part that’s likely to mutate and evolve.
Penaloza-MacMaster’s lab is working on a vaccine that targets proteins “at the guts of the virus,” he said, while other labs are evaluating a nanoparticle vaccine, which features multiple spike proteins from different viruses.
“It’s kind of like throwing the kitchen sink” for the immune system to recognize, Penaloza-MacMaster said.
He added that he hopes Fauci’s endorsement of a universal vaccine pushes the effort forward and spurs more government support.
“In the face of an imminent pandemic, it’s good to have eggs in different baskets. Not every approach will work out,” he said.