These Companies Are Working On Covid Vaccines That Could Stop The Next Pandemic

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Jeff Baxter, the CEO of Cambridge-based biotech VBI Vaccines, was at an all-hands meeting with his staff at the company’s R&D facility in Canada discussing the worsening Covid-19 pandemic. “I remember it vividly,” he says. A staff member “took me aside and grabbed me by the collar and said, ‘Jeff, we have to do something!’” 

The small company, which was incorporated in the U.S. almost 15 years ago, specializes in vaccines for infectious diseases and cancer. But with a market cap of just over $800 million, it couldn’t compete with the other pharmaceutical powerhouses like Pfizer and Moderna, which were able to quickly focus energy on creating a new Covid-19 vaccine. “We weren’t part of the vanguard 5,” Baxter says, referring to the first companies to develop a Covid-19 vaccine, “but we pushed forward.” 

VBI is now leading a new contingent of companies: smaller biotechs that are focused on creating a pan-coronavirus vaccine that can be effective against all variants of Covid-19, as well as coronaviruses that might have pandemic potential in the future. This is a contrast to the “vanguard 5,” whose next-generation vaccines are currently more geared towards booster shots and specific new variants. In March VBI entered a $33 million partnership with the Coalition for Epidemic Preparedness Innovations, also known as CEPI, to develop a pan-coronavirus vaccine that can protect against new Covid-19 variants and other coronaviruses. Clinical trials will start in the second half of this year. 

Half a dozen other companies are charting the same course, hoping to be the winner in this second Covid-19 vaccine race. A vaccine that could protect against all variants of Covid-19 could quickly replace the current vaccines, some of which have shown diminished efficacy against variants first discovered in South Africa and Brazil. But the real prize would be a vaccine that could protect against all betacoronaviruses, the family of viruses that also birthed SARS, MERS and varieties of the common cold. “We’ve seen coronaviruses mutate to be humanly transmissible about every 9 years,” Baxter says. “We need to figure out just how wide we can make those goalposts to cover any novel or mutant strain.” 

VBI’s idea for a pan-coronavirus vaccine is deceptively simple: it plans to train the immune system to be able to recognize a specific part of the virus that exists even on coronaviruses that humans haven’t encountered before. All coronaviruses have a spike protein that is used to enter cells; these proteins create the protruding crown-shape appearance for which the virus is named. “Think of each of those spike proteins as a color,” says David Anderson, chief scientific officer at VBI. You can make antibodies see blue, yellow and red, he says, but you can also “teach the immune system to see something that’s slightly between the blue and yellow, and now you have antibodies that see green.” 

In other words, instead of looking for the exact spike protein that signals a specific coronavirus infection in the body, VBI wants to teach the immune system to be on the lookout for any similar spike protein. “Instead of having a very targeted approach, we’re trying to broaden it,” Anderson says. “There’s ample data out there that says the virus will find a way to mutate,” he continues, and the company also plans to catch it in the event it tries to disguise itself. So far it looks like their approach might work — in animal testing, the company immunized animals with their pan-coronavirus vaccine and looked to see if these antibodies would recognize a betacoronavirus that they hadn’t seen before. Its researchers  chose human coronavirus OC43, the cause of many common colds. Were the new antibodies able to identify it as an infection? “The answer was yes,” says Anderson.

Other companies around the world are also looking for a pan-coronavirus vaccine using different techniques. At Emeryville, CA-based Gritstone, the researchers are focused on not only activating antibodies, but also other parts of the immune system. “If you want to think about a true pan-coronavirus vaccine, you have to go after T-cell immunity,” says CEO Andrew Allen. Canada-based Entos Pharmaceuticals is developing a DNA-based vaccine to protect against all Covid-19 variants. And France-based Osivax is leaving the spike protein alone and targeting a different part of the coronavirus cell, the nucleocapsid, which the company hopes is less prone to mutating.   

While some of these efforts remain in-house, others are supported by non-profit organizations and government funding. In November 2020, the National Institutes of Health issued a Notice of Special Interest to encourage groups working on a pan-coronavirus vaccine to apply for federal funding. CEPI, the organization that has provided funding to VBI for its vaccine candidate, recently offered up to to $200 million in funding to companies that are developing these pan-coronavirus vaccines.


“We don’t really have any true universal vaccines yet.” 

Matt Memoli, NIH

The science behind a pan-coronavirus vaccine seems relatively simple, but many challenges still exist. Scientists have been working for decades to create universal vaccines for influenza and HIV, but so far all efforts have been stymied. When it comes to creating a vaccine that can prevent a multitude of viruses, “there’s nothing per se that’s known to work,” says Matt Memoli, director of the laboratory of infectious diseases (LID) clinical studies unit at the NIH. “We don’t really have any true universal vaccines yet.” 

One of the challenges, says Dennis Burton, a professor of immunology and microbiology at the Scripps Research Institute, is figuring out how broad to make a pan-coronavirus vaccine. The more targeted to one specific variant of a virus the vaccine is, the easier it is to develop. “The wider the net you cast, the more difficult it’s going to be,” he says. “If you want to include all the betacoronaviruses, then it gets a lot more difficult…and then if you want to go for all coronaviruses, that looks very hard indeed, and may be impossible.” 

Another issue: making sure that the vaccine works for people with different immune systems. “You have to make the vaccine able to induce the right antibodies in most people,” Burton says. “That makes it harder, because you’ve got to really be able to make the vaccine independent of genetics.” 

Despite the risk of failure, the potential benefits are enough to keep scientists trying. Experts are convinced that this won’t be the last deadly coronavirus that spills over to humans. “The thing we all live in dread of is a virus that has the infectivity of SARS-CoV-2 with the pathogenicity of MERS,” says Gritstone CEO Allen, “That would be a disaster.” 

Luca Giurgea, an NIH scientist who works with Memoli, describes coronaviruses as “a permanent future risk.” The large reservoir of viruses in bats means that another coronavirus emerging that can infect humans is almost a certainty. But, Giurgea says about universal vaccines, “if you develop a magic bullet, there’s the potential to prevent future pandemics.” 

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