CLEVELAND, Ohio – Over the past several weeks, scientists across the country have announced encouraging developments in the quest to discover a vaccine against the novel coronavirus.
On April 2, the University of Pittsburgh’s School of Medicine announced a vaccine to combat COVID-19 has shown promising results in mice. Days earlier, the U.S. government and pharmaceutical giant Johnson & Johnson committed more than $1 billion to a vaccine co-developed by scientists at Beth Israel Deaconess Medical Center in Boston.
The announcements offer glimmers of hope to millions of Americans living under stay-at-home orders as the coronavirus death toll rises across the country. They carry an important caveat, though, because experts say it could take 12 to 18 months to develop and mass-produce a vaccine for the public.
The process of developing a vaccine is complex because it involves extensive clinical trials to determine if it’s safe. Scientists can use other vaccines as roadmaps for developing one for COVID-19, but it’s ultimately a trial-and-error process, said Dr. Thad Stappenbeck, the chair of the Department of Inflammation and Immunity at Cleveland Clinic’s Lerner Research Institute.
“We have a lot of tools, and a lot of predictive algorithms, but what it really comes down to at the end of the day is you have to try it,” Stappenbeck said. “Some of the things we’re going to try just aren’t going to work. But I think enough things will work, and we’ll be able to develop one or more vaccines that we’ll roll out to the public.”
The timeline offered for the coronavirus vaccine is much quicker than a typical timeframe for a vaccine. Developing an effective vaccine can take as long as 10 to 15 years due to the extensive clinical trial process, experts from the University of Maryland’s Center for Vaccine Development and Global Health (CVD) said during a Thursday discussion sponsored by the National Press Foundation.
Only 5 to 10 percent of vaccine candidates are successful, usually, because they don’t produce the desired response from a body’s immune system, said Dr. Kathleen Neuzil, the director of the CVD. Experts are hopeful the sheer number of candidates presently in production could lead to a breakthrough.
“We want a lot of shots on goal right now, hoping we’ll score with at least one of these,” Neuzil said.
How does a vaccine work?
Vaccines typically introduce an inactivated form of a virus or bacteria into the body to trigger an immune response. Scientists can also use certain parts of a virus or bacteria, or their genetic material. The body responds by creating protective proteins called antibodies that latch onto the virus or bacteria to destroy them.
“You basically introduce it, your body’s immune system sees it, and it will trigger an immune response that will hopefully be lifelong,” Stappenbeck said.
It’s unclear if a COVID-19 could provide permanent immunity to the virus. Vaccines for previous coronaviruses have offered temporary protection, so it’s possible people could need it more than once, like an annual flu shot.
Even temporary immunity against the coronavirus would be a welcome development, experts said, because doctors have not discovered a proven treatment.
“When you’re in the middle of a pandemic, you’re happy to settle for six months of protection,” Neuzil said.
Multiple approaches to building a vaccine
Traditionally, researchers have developed vaccines using inactivated forms of a virus. The novel coronavirus is so dangerous, though, that scientists are using other methods.
Advances in technology make other approaches possible. One method involves extracting the genetic code for the spike proteins on the surface of COVID-19. That part of the virus is most likely to cause the body’s immune system to react, experts say.
“Spike proteins are kind of the business end of the virus,” Stappenbeck said. “These allow the virus to interact with susceptible host cells in the lungs and the gastrointestinal tract.”
Moderna Inc. of Cambridge, Massachusetts, is using messenger RNA, or mRNA, to develop a vaccine. Messenger RNA carries genetic information from DNA and is used to produce proteins. Moderna is using mRNA to carry the genetic sequence of the coronavirus to the body so it can produce antibodies.
Maryland-based biotech company Novavax developed an antigen, or a toxin, derived from the spike protein. The company is combining it with an adjuvant, which makes a vaccine work better, to enhance the body’s immune response.
“I think the depth and breadth of the strategies that are being taken are important because not all of these are going to work,” Stappenbeck said. “Developing a vaccine to a new pathogen is really an inexact science.”
An exhaustive clinical trials process
Once a vaccine is created, it must go through comprehensive clinical trials before it is available to the public. Moderna and Norovax have already announced plans to test their vaccines through clinical trials.
Experts said the clinical trial phase could take more than a decade, but there are extensive efforts to reduce that timeline for COVID-19.
“When we have a pandemic, we try to truncate anything,” Dr. Wilbur Chen, and adult infectious disease expert with the University of Maryland’s CVD, said during the Thursday discussion.
During the first phase of a clinical trial, a vaccine is injected into a small group of volunteers. Scientists are trying to determine if the drug is safe, so they monitor those volunteers for any adverse side effects. Scientists also try to determine the correct dosage for the vaccine.
Once scientists determine a vaccine is safe, they try to decide whether it’s useful. The second phase of clinical trials involves more volunteers, so there is a more significant chance scientists could see rare side effects. If those side effects are relatively mild and the drug appears to be effective, it can move to phase three.
During the final phase, the vaccine is administered to thousands of people, to determine its effectiveness and safety.
It’s difficult to say which of the promising coronavirus vaccines may make it through clinical trials. But Stappenbeck believes medical experts are so focused on developing a COVID-19 vaccine that one is bound to be effective.
“Some of the early frontrunners here may pan out, or may not pan out,” Stappenbeck said. “So I think some of it is just letting a substantial number of these trials get going, so we can see which ones are actually going to become valuable.”
Regulatory approval and mass-production
Once the clinical trials finish, the results are submitted to the U.S. Food and Drug Administration for approval. The process involves a new drug application, pre-licensure reviews, a license application, an inspection of the facility where the vaccine will be manufactured, and a formal presentation to an FDA advisory committee.
The FDA continues to monitor vaccines once they’re approved for the general public, in case any adverse side effects surface.
After a vaccine is approved, it must be mass-produced and shipped so it for use in the general public. That could take time, but there are efforts to speed up the process.
Dr. Anthony Fauci, the director of the National Institute of Health, has announced that a vaccine developed by NIH scientists could go into production before clinical trials finish. It it’s effective, they’ll have a head-start on production; if it fails, they’ll have to scrap any vaccines they’ve produced.
Stappenbeck said he’s optimistic that the breadth of research for a coronavirus vaccine may accelerate the timeline for administering it to the public. Even still, he said speeding up the process takes a backseat to ensure a vaccine is effective and safe.
“I think it should be comforting to people that the scientific community is taking this extremely seriously,” he said. “A lot of the best minds in the world in vaccine development are working on this.
“They’re trying to make it as fast as possible,” Stappenbeck said. “But they have to still be safe.”
Cleveland.com reporter Emily Bamforth contributed to this story.