CLEVELAND, Ohio — When University Hospitals needed volunteers willing to test an experimental vaccine for COVID-19, UH’s Dr. Margaret Larkins-Pettigrew signed up, and brought along her physician husband as well.
The couple learned they will undergo two injections of either the vaccine or a placebo; they won’t be told which they were given.
Over the next two years, they will undergo periodic physicals, keep track of their symptoms and turn over their medical records to trial organizers if they are hospitalized for COVID-19.
Larkins-Pettigrew said she felt an obligation, as a physician, to participate in the vaccine trial.
“This is a safe trial to be involved in,” said Larkins-Pettigrew, who is UH Edgar B. Jackson chair of Clinical Excellence & Diversity. “Science will direct us to make sure all of us are protected.”
All over the world, people like Larkins-Pettigrew are signing up to help pharmaceutical companies test prospective COVID-19 vaccines, as part of an effort to get vaccines to the public and stop the pandemic’s devastating effect.
In Ohio, Pfizer and its partner BioNTechSE, and Moderna — forerunners in the race to develop a vaccine — are conducting trials at research centers across the state to determine their safety and efficacy.
Ohio State University Wexner Medical Center is the site of a two-year, Phase 3 trial of the vaccine developed by AstraZeneca, a British-Swedish company, and the University of Oxford.
University Hospitals and the Louis Stokes Cleveland VA Medical Center are among 120 clinical investigational sites around the world that will collectively enroll up to 44,000 participants in a Phase 3 trial to test the vaccine BNT162b2, developed by Pfizer and the German company BioNTechSE.
Rapid Medical Research Inc., in Beachwood is testing the mRNA-1273 vaccine from Moderna in a two-year trial. Two sites in Cincinnati are also testing this vaccine.
How much protection will these vaccines offer? Will we need to get a coronavirus shot every year?
“These are all open questions,” said Dr. Carlos Malvestutto, assistant professor of infectious disease and co-chair of the COVID-19 Task Force, at Ohio State University Wexner Medical Center.
“The only way to answer them is through clinical trials,” Malvestutto said.
The public has questions as well, such as how these vaccines work inside the body, why some trial participants receive a placebo and how to join a trial.
Let’s get some answers.
How do these vaccines work?
All vaccines trigger the body’s immune system to mount a defense against invading illnesses. The approach taken by AstraZeneca is different from how Pfizer and Moderna are approaching the problem.
AstraZeneca’s vaccine uses a modified chimpanzee adenovirus, altered to make it harmless to humans, Malvestutto said. The adenovirus is used as a viral vector to carry a single coronavirus gene into the body. The coronavirus components of the vaccine spark an immune response against the actual coronavirus.
The vaccine does not include the whole virus and cannot cause COVID-19, Malvestutto said.
The Pfizer vaccine candidate is made up of messenger RNA coupled to a protein from the coronavirus, said Dr. Robert Salata, program director for UH Roe Green Center for Travel Medicine & Global Health.
Messenger RNA, or mRNA, are molecules that tell cells what to produce. Messenger RNA vaccines direct the body to produce specific kinds of antibodies.
The Pfizer vaccine candidate being tested at UH uses a synthetic mRNA that carries instructions for making coronavirus spike proteins, the projections that give the virus its crown-like appearance. The presence of the mRNA spike proteins tricks the body into thinking it is already infected with COVID-19, so it produces antibodies and T-cells in response. T cells play a central role in the immune response.
The AstraZeneca, Moderna and Pfizer vaccines will be given in two injections, with the second shot administered a few weeks after the first. One shot will likely provide some protection against COVID-19, but two shots are more effective, Salata said.
Why was the AstraZeneca trial put on hold?
AstraZeneca paused its trial in early September to review safety data because a trial participant in the United Kingdom was diagnosed with transverse myelitis, or spinal cord inflammation. Transverse myelitis can be a post-infectious complication due to viral, bacterial or even parasitic infections, Malvestutto said. The company confirmed that the patient received the vaccine and not a placebo.
The Phase 3 vaccine trial has resumed in the U.K., South Africa and Brazil. The FDA and the study Data and Safety Monitoring Board are still reviewing the data about this adverse event and enrollment in the U.S. remains on hold pending the completion of that review, Malvestutto said.
Pausing drug trials because of an adverse event is standard, Wexner’s Malvestutto said. “This is exactly what is supposed to happen. Safety is paramount,” he said.
What is a double-blind, randomized placebo trial?
All of the trials taking place in Ohio are double-blind, randomized placebo trials.
Double-blind means that neither volunteers nor researchers know which test subjects receive the vaccine and which get a placebo. A computer randomly assigns test subjects into each group.
Later in the trial, information about which participants received the drug is released to the researchers, UH’s Salata said.
“This is the best type of setting to measure the true effectiveness,” Salata said.
These trials will look at the occurrence of cases of COVID-19 in the vaccinated and placebo groups, and determine if vaccinated people who got COVID-19 had a milder form of the illness.
It’s not ethical to deliberately expose trial participants to COVID-19, especially since there is no effective treatment yet. But all trials are enrolling large numbers of people to increase the chance that enough of them will develop the illness through community spread, Salata said.
These local trials are recruiting people who have some risk of exposure in their daily lives, such as healthcare workers and first responders. These studies also want to enroll a representative percentage of African Americans and Latinos, to ensure that the vaccine is effective among those communities hard-hit by COVID-19.
After receiving the placebo or vaccine, volunteers will be asked to make in-person visits with research physicians and record symptoms with a diary or app.
Most trials pay volunteers a stipend for travel and other expenses.
Volunteers in Wexner’s AstraZeneca trial receive about $600, and an additional $300 if they are diagnosed with COVID-19. The UH trial pays $120 for each vaccine visit.
What is a Phase 3 trial?
Clinical development of new drugs or vaccines is a three-phase process, according to the Centers for Disease Control and Prevention. In Phase 1, small groups of people receive a trial vaccine. In Phase 2, the trial vaccine is given to people who have characteristics similar to those for whom the new vaccine is intended.
In Phase 3, the vaccine is given to thousands of people and tested for efficacy and safety. Data is submitted to the Federal Drug Administration for approval of the drug.
How effective will these vaccines be?
The FDA wants any COVID-19 vaccine to offer at least 50% effectiveness in protecting against the illness, said Dr. David Canaday, the Cleveland VA’s Geriatric Research Education Clinical Center (GRECC) associate director of research.
That would make the COVID-19 vaccine as protective as the most effective flu shots, Canaday said. The flu vaccine fluctuates between 15% and 60% efficiency from year to year, he said.
Even if the flu shot doesn’t prevent you from getting the flu, it can mitigate the illness so you miss fewer days of work on school. The same may be true of the COVID-19 vaccine, Canaday said.
What are the drawbacks?
Volunteers in the AstraZeneca trials said they felt some pain in the area where they received the injection, mild fever, muscle aches and chills, according to a paper published in the Lancet in July.
Five participants in various parts of the country — three in Moderna’s study and two in Pfizer’s trials — recently told CNBC that they experienced severe chills, high fever, body aches, bad headaches and exhaustion after receiving the shots.
Researchers are paying close attention to unexpected side effects, especially any that lead to hospitalizations, Malvestutto said.
“There’s almost no chance the vaccine will work on 100% of people,” which is true of all vaccines, said Dr. Tim Chan, director of the Center for Immunotherapy and Precision Immuno-Oncology at the Cleveland Clinic.
Older people, who have a lowered ability to produce antibodies, as well as people at high-risk for COVID-19, may need to take a combination of COVID-19 vaccines, Chan said.
Future studies will be needed to determine if these people will need a combination of the vaccines currently in development, or if a second generation of COVID-19 vaccines will be needed to protect them, Chan said.
How can volunteers apply?
Wexner Medical Center trial: Apply at the Coronavirus Prevention Network website.
UH trial: Call 612-524-9091.
Rapid Medical Research: Call 216-508-4400 or email [email protected]
Recruitment for the VA Medical Center trial is on hold because it has reached its allotted number of participants.
When could these vaccines be ready?
Pfizer expects to have data from the trial as early as the end of this month, although the trial will continue. Pfizer has promised to deliver 100 million doses to the federal government by the end of the year, if it’s successful, Salata said.
AstraZeneca has said it hoped to have a vaccine ready before the end of the year, according to published reports.
Moderna announced this week that its experimental COVID-19 vaccine is not expected to be available to the public until spring.
However, two recent developments may slow down the journey towards a vaccine:
The FDA announced tougher rules for authorizing any COVID-19 vaccine on an emergency basis. Also, Operation Warp Speed, the government’s vaccine fast-tracking effort, advised pharmaceutical companies not to apply for emergency use authorization until they have significant amounts of vaccines on hand.
These developments could push the first authorization into mid- to late November, press reports said.