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Here’s what four Colorado research teams have learned from working on a coronavirus vaccine

Three different labs at Colorado State University and a team from the company Greffex are all taking different approaches to developing a vaccine for COVID-19

A researcher at Fort Collins-based BioMARC holds up samples of culture material that represent the starting place for growing out large viral stocks on October 9, 2014. BioMARC, which manufactures vaccines, is working with scientists from CSU's Infectious Disease Research Center on a vaccine for COVID-19. (Provided by Colorado State University)
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As Colorado slogs into its third month of the coronavirus pandemic, there is new hope around the globe that somebody, somewhere is getting close to developing a vaccine that would make this interminable misery actually terminable.

Multiple vaccine candidates have launched into human trials in the last couple of weeks — the most recent being a trial by the drugmaker Pfizer, which on Monday started poking needles into healthy volunteers in New York and Maryland. The White House has picked 14 vaccine candidates for a project it has dubbed “Operation Warp Speed,” a name that encapsulates the gonzo-scientific, just-crazy-enough-to-work pace at which vaccine development is taking place.

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But, as this research charges furiously ahead, there is also growing skepticism that it’s going to end well or, at least, soon. Humankind has never successfully produced a vaccine against any type of coronavirus, much less a brand new coronavirus variant. Previous efforts have been shown to cause harm in their test subjects or lost their funding when the virus they were targeting abated.

“The reality is that the majority of vaccines will fail,” said Dr. Gregg Dean, a veterinarian and professor at Colorado State University who studies viruses. “So it’s really important that we have as many groups as we do with all their different ideas and hopefully one or a couple of different groups will get it right.”

Scientists in Dean’s lab are among at least four teams in Colorado currently working on developing a vaccine against COVID-19, the disease caused by the coronavirus. (The virus, itself, is known scientifically as SARS-CoV-2.) In the handful of weeks that they have all been hard at work on the challenge, here’s what they’ve learned:

Dr. Amy MacNeill, associate professor of microbiology immunology and pathology at Colorado State University, researches a possible vaccine for COVID-19 at the university’s Veterinary Diagnostic Laboratories i Fort Collins on May 1, 2020. (Provided by Colorado State University)

The more approaches, the better

There are at least 115 COVID-19 vaccine candidates in development across the world right now.

They all attempt to do the same thing — induce the body’s immune system to produce antibodies that can fight off an infection by the coronavirus. But they have different methods for what goes into a dose of vaccine. Some deaden the real-deal virus; some synthesize just a bit of that virus; and some hijack other viruses.

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Typically, the researchers aren’t starting from scratch. They have been working in vaccine development for years and have quickly pivoted their existing methods to create a vaccine for the coronavirus.

In Colorado, each of the four teams is trying a different approach:

  • The old-school: Raymond Goodrich’s team at Colorado State University is developing a vaccine using inactivated SARS-CoV-2 virus. The method inactivates the virus by running it through a machine that Goodrich invented to purify water. After being inactivated, the virus can’t replicate inside people, so it’s essentially just a punching bag for the immune system.
  • The yogurty: Ever looked on the side of a yogurt container and seen that it contains the beneficial probiotic bacterium Lactobacillus acidophilus? That’s also the key to the vaccine Dean’s team is developing. The team is genetically modifying the bacterium to grow the signature “spike protein” that rings SARS-CoV-2 and allows the virus to unlock human cells. Like roundhouse kicking your karate instructor, this allows the body to train for self defense against a friendly foe.
  • The poxy: A ton of the work being done on a coronavirus vaccine involves “viral vectors” — that is, different viruses that can be hollowed out and modified to look like the coronavirus. Basically, they’re target dummies. Dr. Amy MacNeill, a veterinary pathologist at CSU who studies how to use the immune system to fight cancer, is working on one such vaccine using a modified form of a poxvirus.
  • The nimble: At a lab right across the street from the Anschutz Medical Campus in Aurora, the Houston-based company Greffex works to develop vaccines against dozens of emerging infectious diseases. Greffex uses a highly customized version of an adenovirus as its platform, which allows it to quickly develop new vaccines, said CEO John Price. The company announced it had created its coronavirus vaccine candidate all the way back in mid-February.

MacNeill said it’s important to have many different options in vaccine development. Some might work better for some people than others. There are manufacturing, transportation, storage and price concerns to think about.

“I think of it all as being complementary to each other,” she said. “I hope that one of the ones that’s really advanced will be the one that helps everybody and makes it go away. But chances are it will be helpful to have multiple vaccine platforms available.”

This is a 3D print of a SARS-CoV-2 virus particle. SAR-CoV-2 is the coronavirus that causes COVID-19. The virus surface (blue) is covered with spike proteins (red) that enable the virus to enter and infect human cells. (Provided by the National Institutes of Health)

It’s OK to go slow(ish)

All of the research teams working in Colorado right now agree on something: They probably won’t be the first to develop a vaccine ready for widespread use. And, they also agree, that’s not a bad thing.

“This isn’t an arms race,” Price said.

Quite often in vaccine development, the frontrunners aren’t the most ideal. For instance, they may require one or more booster doses. They may need to be refined to create a stronger immune response. And, in the meantime, it’s important for researchers to understand the vaccine’s effects.

Let Dean introduce you here to the concept of “antibody-dependent enhancement.” Sometimes, Dean said, a vaccine can induce the body to produce antibodies that actually help the virus gain entry into human cells.

If you think of a lock-and-key metaphor, viruses contain keys that allow them to unlock human cells. Antibodies grab hold of those keys and block them. But what if another part of that antibody is itself a key that can unlock a cell? It’s been a persistent problem in work to develop a vaccine for feline coronavirus, he said.

“It’s a normal part of the immune system,” he said. “But in this case, the virus can take advantage of that and use it to sneak into those cells using a different receptor.”

Gregg Dean, department head and professor of Microbiology Immunology and Pathology at Colorado State University, is working to develop a vaccine for the COVID-19 virus. Photographed March 31, 2020. (Provided by Colorado State University)

So, taking this measured approach, all of the Colorado research teams are still relatively early in the development timeline.

Goodrich’s team, which includes veteran infectious disease researcher Dr. Richard Bowen, is about halfway through a 10-week test of its candidate in hamsters. Dean and MacNeill are working to construct their vaccine candidates before moving into tests in animals.

Greffex is the furthest along, with Price saying that his team is about eight to 10 weeks away from entering clinical trials with a target date of completing its work by the end of the year. But Price reiterated the first across the finish line isn’t the prize here.

“It doesn’t matter,” he said. “Get them all successful and make sure you know how to manufacture them.”

Raymond Goodrich, left, the director of the Infectious Disease Research Center at Colorado State University, talks with U.S. Sen. Michael Bennet during a tour of CSU’s Research Innovation Center on March 6, 2020. (John Ingold, The Colorado Sun)

There’s value in the research, regardless

Even if the Colorado vaccines aren’t first — heck, even if they turn out not to work — each of the research teams say there is still value in the work.

There’s still a lot we don’t know about the coronavirus and how the immune system responds to it. That makes every study and every vaccine project currently underway valuable, Goodrich said.

“If the problem gets solved before we get to the finish line — and I hope it does — all of the knowledge that we’re gaining, all of the experience we’re gaining is going to be useful when another pandemic arrives,” he said. “Maybe that knowledge will help us not only respond to the next pandemic but will help us prevent the next pandemic from occurring.”

MacNeill said the research being done by one team will help inform the work of other teams. Vaccines could eventually be combined in a single dose to enhance efficacy. And it’s not just humans who could benefit from a vaccine — with evidence growing that some animals can also be infected by SARS-CoV-2.

“Maybe my vaccine will never go into people but it will be the one that gets all cats vaccinated,” she said.

Staff at Fort Collins-based BioMARC operate a bioreactor that is used to grow large volumes of virus for scale-up production of vaccine candidates. BioMARC is working with scientists from CSU’s Infectious Disease Research Center on a vaccine for COVID-19. (Provided by Colorado State University)

This can be done

So, to the big question: Can we actually develop a successful vaccine for COVID-19? Every one of the Colorado researchers says yes.

“I honestly believe we’re still on target,” Price said of his company’s candidate.

Dean talked about the massive coming together of the scientific community to focus on this one virus. Literally all of the world’s best minds in medicine and biology are currently working on vaccines or treatments to stop the pandemic.

“What I see is that scientists are doing everything they can to work together and quickly share information,” he said.

Goodrich pointed to promising results from a team at Oxford University that inoculated a half dozen rhesus macaques with their vaccine candidate and then bombarded the monkeys with live coronavirus to no avail.

And MacNeill noted promising research recently published on vaccines for MERS, a respiratory disease caused by a different coronavirus. Somebody’s going to figure this out, she said. This is within human capability.

“I think that we can get it done and I think we can get it done much more quickly because of what we know from similar coronaviruses,” she said. “I think, with what we know about the biology of the virus and how it gets into cells, we should be able to stop that.”


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