Over the last several months, the COVID pandemic has become an exercise of vaccination whack-a-mole.
A variant arises, and the vaccine manufacturers figure out how to tweak their product to address it — but not quickly enough. New variants keep arising, making the variant-specific shots outdated before we even get a chance to use them.
But what if scientists could develop one universal vaccine that could address all variants? That work is underway at academic labs and biotech firms, including several in Boston, and in recent months, progress has picked up speed.
The National Institutes of Health has awarded about $43 million to four academic teams developing broadly protective coronavirus vaccines. And the Coalition for Epidemic Preparedness Innovations (CEPI), a foundation that funds work on vaccines for emerging infectious diseases, has awarded up to $135.2 million to seven groups — mostly small biotech firms — developing similar shots.
But despite the investment, it will likely take longer to develop pan-coronavirus vaccines than it did for the original COVID-19 shots.
Years of research on other coronaviruses enabled scientists to tailor-make those vaccines in a matter of weeks. The US government’s multibillion-dollar Operation Warp Speed program then fast-tracked the clinical testing and manufacturing of those shots in under a year.
“I think it would really be a little bit of a stretch to say that we would have it in the fall or winter,” Fauci said.
Part of the problem is that there are at least seven coronaviruses known to infect humans and hundreds more known to infect animals. The coronavirus family tree is huge, said Florian Krammer, an immunologist at the Icahn School of Medicine at Mount Sinai in New York, who recently critiqued plans for a universal coronavirus vaccine as unrealistic. “Making a vaccine against all of those is really a tough challenge,” Krammer said.
As disruptive as SARS-CoV-2, the virus that causes COVID-19, was to our lives, it’s only a small set of twigs on a far-out branch of the enormous coronavirus family tree. Fauci said that talking broadly about universal coronavirus vaccines “is really a little bit aspirational and potentially misleading.” There are many coronaviruses, and we don’t necessarily need a vaccine that protects against all of them.
The most near-term goal would be to create a variant-proof vaccine that protects against all existing and future variants of SARS-CoV-2. The next step could be to make shots for sarbecoviruses, a branch of the coronavirus family tree that includes the viruses that caused SARS and COVID-19, plus related bat coronaviruses that all use the same receptor to infect cells.
An even more ambitious goal would be to create a vaccine for all betacoronaviruses, a sprawling branch of the family tree that includes the sarbecoviruses and four other clans, including the one that causes MERS, or Middle East Respiratory Syndrome.
But different clans of betacoronaviruses use different receptors to sneak into cells, which means the shape and structure of the viruses are different.
“It’s not very realistic to make a vaccine that would protect against all coronaviruses or all betacoronaviruses,” said Pamela Bjorkman, who studies the structures of viruses at Caltech. “It’s just a bunch of hype.”
But a vaccine that protects against at least some of those viruses, particularly variants of SARS-CoV-2 and its closest cousins, may be in reach.
There are two main ways of thinking about making variant-proof vaccines. One is to simply show immune systems spike proteins from multiple variants or even multiple coronaviruses. Scientists hope that those molecules could train immune systems to generate “a broad enough response that you will cover most if not all of the potential variants,” Fauci said.
Several groups are pursuing their own versions of that approach, including Cambridge-based Affinivax and VBI Vaccines, which are each developing shots based on distinct technologies that display spike proteins from multiple coronaviruses on a single particle. And Bjorkman’s Caltech lab has made a nanoparticle studded with crucial portions of the spike protein from eight betacoronaviruses.
A second strategy for making pan-coronavirus vaccines is to design a shot that takes aim at areas of the virus that are least likely to mutate.
Early in the pandemic, Dr. Gaurav Gaiha, a researcher at the Ragon Institute of Massachusetts General Hospital, MIT, and Harvard University, pinpointed those potential weak spots in SARS-CoV-2. As new variants continued to emerge, few or no mutations popped up in those critical regions. “We feel very confident that these regions are not going to change,” he said.
All approved COVID-19 vaccines are based on the spike protein, which antibodies target to neutralize infections. But the weak spots that Gaiha’s lab found were largely in other parts of the coronavirus and are targeted by T cells, another important part of the immune system.
“[T cells] can target the entire SARS-CoV-2 virus, not just the spike protein,” Gaiha said. He is working with Cambridge biotech firm Codiak Biosciences to make vaccines that teach T cells to target the virus’s weak spots.
While antibodies are important for preventing infections, T cells can help remove infected cells from the body and prevent a mild disease from becoming severe.
Some researchers are trying to refine our understanding of how immune systems respond to the coronavirus as a steppingstone to making better vaccines. “Part of our project is to look at people who have made very good responses from natural infection or vaccination and try to learn from them,” said Dr. Andrew Luster, chief of the Division of Rheumatology, Allergy and Immunology at Mass. General.
Luster and his colleague Dr. Duane Wesemann, an associate physician at Brigham and Women’s Hospital, have a pan-coronavirus vaccine grant from NIH to systemically study ways to increase the breadth and durability of the immune response to coronaviruses.
“The holy grail is to get a vaccine that is universal. But that has also been the holy grail for HIV and flu and we have yet to see it in those cases,” Wesemann said. A pan-sarbecovirus or pan-betacoronavirus vaccine “theoretically is possible, but I am not sure that is even going to come in the next five to 10 years,” he added. “It is going to take time; it is not an easy problem.”
Jonathan Saltzman of the Globe staff contributed to this report.