Racing to discover a coronavirus vaccine
3 ASU researchers join global fight to stop contagion
Just three days after a case of the new coronavirus was confirmed at Arizona State University, Brenda Hogue huddled with two other university researchers inside the school’s Biodesign Institute.
It was a battle strategy meeting. Their weapon would be a vaccine and the target was the new virus.
Playing on each of their strengths, they came up with a three-pronged approach to make different vaccines for the new coronavirus and see what works best.
As a researcher focusing on coronavirus, Hogue will provide general expertise and develop one of the three vaccines using mammal cells.
Meanwhile, molecular biologist Qiang “Shawn” Chen and virologist Bert Jacobs plan to develop their own vaccines using different techniques. Jacobs will change an existing vaccine to try to target the new coronavirus and Chen
“The challenge is timing because people are being hurt by this virus.” Qiang “Shawn” Chen ASU molecular biologist
will use plants to create a vaccine that he hopes will be more potent than those made in mammal cells.
They are joining a global race to combat the virus, which has infected over 60,000 people, mostly in China, and has killed over 1,300. The U.S. currently has 14 confirmed cases in six states, including Arizona. The spikes overseas are at least partly due to new counting standards implemented by China, which reported Wednesday that it is tallying infections differently.
Researchers working around the world must contend with the virus’s rapid spread since it was first detected in Wuhan, China, in December 2019, and a lack of knowledge about how exactly the virus is spreading and how lethal it is.
Making a vaccine isn’t a straightforward process. Vaccines can have adverse side effects, can be expensive to make, often take years to get approved or may simply not work.
Hogue and her colleagues are later to the race than others, like the researchers at the National Institutes of Health who have clearance to expedite their development process. But the ASU team believes it’s critical to have backup options for a vaccine, in case other researchers falter or a better vaccine is possible.
“We know it is a highly competitive field but we don’t know which strategy will be effective and safe for use in humans,” Hogue said.
Regardless of whether they succeed in finding a vaccine for the new coronavirus, Hogue said it’s likely there will be more coronavirus strains and outbreaks in the future, so research could potentially be used in the hunt for the holy grail: a universal coronavirus vaccine.
Before Hogue and her team can begin their research, they need a copy of the genes — in this case, the RNA — from the new coronavirus. The problem is that a lot of other researchers are trying to get their hands on the same thing, creating a bottleneck for resources.
The team at ASU could get the genes within a week, or it could take a little longer than a month.
“We’re all trying to do what we can to respond,” Jacobs said. “We believe that once we get the RNA we can have a vaccine within a month or month and a half.”
The other challenge is funding. Developing a vaccine can cost hundreds of thousands of dollars before it can be manufactured for general use, and one big source of funding is usually the National Institutes of Health.
Hogue, Jacobs and Chen have put together a proposal to submit to the NIH but unless the institute puts out a special call for proposals, any funding, if it’s approved, won’t come for another six months.
Waiting six months to start research isn’t an option, the researchers say.
“The challenge is timing because people are being hurt by this virus,” Chen said.
The team is drawing on whatever discretionary funding they may have, from other research projects or personal funds, and they are getting some university money to generate the tens of thousands of dollars they need to start research.
“I believe the work I’m doing is good work,” said Jacobs, who is partially using his own personal money for the project.
The severity of the new coronavirus within China means the NIH and other organizations will likely dedicate a lot of money toward combating the problem, but to get funding, Chen, Hogue and Jacobs must submit a competitive proposal.
With their three-pronged approach, Chen said he is confident they can get funding for their research, but they are unlikely to be the first ones to develop a vaccine for human use.
At least a dozen research teams globally have already made headway in vaccine research against the new coronavirus.
The Coalition for Epidemic Preparedness Innovations, a global organization that supports vaccine development against emerging diseases, announced in late January they would be supporting three major vaccine efforts.
Two of efforts focus on a related, severe strain of coronavirus within the coronavirus family called Middle East Respiratory Syndrome, or MERS. The third, which involves the National Institute of Allergy and Infectious Diseases, part of the NIH, is focused on developing a vaccine targeted at the new coronavirus.
That project is moving at breakneck speed, with a goal of testing the vaccine in humans within three months, a swift progression compared to the normal time of at least 20 months.
Dr. Anthony Fauci, director of the NIAID, said they are on track to test their vaccine by April.
“Whenever you’re dealing with a vaccine, there’s always a potential for glitches,” he said. “Right now, all those glitches, they’ve been overcome.”
Phase one of human testing will still take at least three months to complete, he said. Then a decision has to be made about whether the vaccine will advance to a phase two trial.
“The risk is the companies now have to invest a lot of money,” Fauci said. “You would have to do a trial of several hundred to several thousand people to see if it works — that usually takes anywhere from several months to a couple of years.”
Even with expedited approval, phase two of the new coronavirus vaccine would require a time investment of at least a year, he said.
By that point, there is a chance that the virus could be contained, just like a similar strain of coronavirus known as Severe Acute Respiratory Syndrome, or SARS. It infected over 8,000 people in 2003 after emerging in Asia and caused over 700 deaths during the first year of the outbreak, but died out in 2004 before researchers could develop a vaccine against it.
“If it had not been contained, then we would likely have a vaccine today against SARS and that would’ve expedited (a new vaccine) even better,” Hogue said.
There is always a chance that the NIAID’s or other researchers’ vaccines may not work well in humans. That means Hogue, Chen and Jacobs could still be first to come up with a good vaccine. While that’s a goal of theirs, the priority is still helping people, Jacobs said.
“It’s not really a competition, we all want to get something to work, Jacobs said. “The first vaccine we make will probably not be optimal for anybody but then we can build on the vaccine we already have to make something better.”
To make a more effective vaccine, the ASU team developed a unique approach.
Instead of working directly with the new coronavirus, Hogue’s strategy depends on creating what she calls “viruslike particles.” These particles are essentially empty shells of the virus that look the same and have the same parts, but lack the genetic “guts” that make the virus infectious.
The shells can be injected into a host to train the host’s immune system to respond to these types of particles. When the immune system sees another particle that looks the same — in this case, the new coronavirus — the body will know how to attack it.
Unlike bacteria, viruses and viruslike particles can’t be grown in a petri dish. A virus always needs a host cell to survive. So for one prong of the vaccine development strategy, Hogue will be using mammal cells to create the particles, then will inject mice with them and measure the mice’s immune responses.
She used a similar technique against SARS back when the outbreak occurred in 2003.
“For any of us that were around when SARS appeared, it’s similar,” she said. “But this time is different because of a larger number of people infected in China.”
Her SARS vaccine was tested with success in mice, but because of a lack of funding and priority for SARS research after the outbreak died down, she never advanced to the next stage of testing, which would have been to “challenge” the vaccine by checking to see if it protects mice from infection.
To get approval for human trials, Hogue needs to demonstrate the safety and success of any vaccine in animals first.
Her colleague, Chen, is conducting a similar approach, except he will use plant cells to create the virus shells instead of mammal cells. This provides a few advantages.
“For mice to produce an immune response they have to see something foreign, and the shells produced from plants are more foreign than the ones in mammal cells,” Chen explained.
Chen has extensive experience with this method in researching vaccines for Ebola, Zika and West Nile Virus. In addition to producing a more potent and effective vaccine, Chen said using plants can also lower production costs and increase safety.
“Our system is really fast and flexible, so it’s perfect for these types of unpredicted outbreaks,” he said.
The third prong of attack is through Jacobs, who will genetically modify a smallpox vaccine known as vaccinia in order to target the new coronavirus.
For years, Jacobs has genetically modified vaccinia to create vaccines for other diseases, such as HIV.
In this case, he will put the new coronavirus’s “spikes” on the existing vaccine. The spikes stick out from the surface of the new coronavirus particle and are responsible for interacting with host cells to cause infection.
By putting the spikes on his smallpox vaccine, Jacobs hopes to train the immune system to respond to the spikes and destroy any particle that has them, thus preventing infection from occurring.
The vaccines that Hogue, Chen and Jacobs develop will not stand on their own. Jacobs said to get the strongest vaccine treatment, the team may combine his vaccine with Chen’s.
For now, Jacobs, Chen and Hogue will continue working around the clock.