Propelled by encouraging results from early experiments, the clock has ticked forward one hour since June in USA TODAY’s countdown to a vaccine against COVID-19. For July, the hands sit at 5 a.m., our panel of experts estimates.
Midnight is the starting point of the pandemic in the USA, and noon is the time a vaccine will be widely available to Americans, so this race is far from over.
“These first steps simply mean that we haven’t fallen at the first hurdle,” said Dr. Kelly Moore, associate director of immunization education with the Immunization Action Coalition. “That doesn’t change the number of hurdles ahead.”
To understand when pre-COVID-19 life in the USA can resume, USA TODAY created a panel of experts in medicine, virology, immunology, logistics and supply chain issues to estimate how close we are to securing a vaccine against SARS-CoV-2, the virus that causes COVID-19. Every month, these experts will track progress and highlight inevitable setbacks.
The panelists were pretty much in agreement in June: We were about one-third of the way. This month, opinions turned out to be more diverse – estimates ranged from a cautious 1 a.m. to an optimistic 8 a.m. The median response or midpoint of the more than a dozen experts was 5 a.m.
Some were more cautious about the science, the many unknowns and what could go wrong. Others were concerned public opinion might drag out clinical trials if not enough volunteers sign up or make people hesitant to get a vaccine if and when one becomes available.
“A lot has to go right,” said Paul Offit, director of the Vaccine Education Center at Children’s Hospital in Philadelphia. “You have this enigmatic, difficult-to-characterize, elusive virus that you’re trying to defeat. Let’s assume the surprises we’ve had so far are not the end of surprises – it’s not unreasonable to assume there will be more surprises down the road.”
The virus emerged eight months ago, a blink of the eye in the millennia-long struggle between humanity and microbes. More than 617,000 people have died worldwide, more than 142,000 of them in the USA.
Early clinical trial data from three candidate vaccines – by Oxford/AstraZeneca, Moderna and Pfizer – shows them to be safe so far and to spur immune responses in healthy adults. Billions of U.S. tax dollars have been allocated to create a vaccine, including nearly $2 billion to Pfizer on Wednesday. Several other candidate vaccines in China are progressing through trials, one of which is being tested in soldiers.
Data on whether the candidate vaccines protect against illness, and for how long, won’t come until large Phase 3 trials, slated to start as soon as this month, begin returning results this fall.
The positive early trial findings fuel optimism. “At least the first goal of any vaccine to induce neutralizing antibodies is met, which is better than a vaccine failing to trigger sufficient antibodies,” said Prakash Nagarkatti, an immunologist and vice president for research for the University of South Carolina.
Florian Krammer, a virologist at the Icahn School of Medicine at Mount Sinai in New York City, said he’s upbeat about a vaccine being ready soon.
“There is pretty good data out there,” he said, and more coming soon. “I am pretty optimistic! As long as there are no shortcuts in the Phase 3 trials…”
Coming soon: Phase 3 Clinical Trials
The final – and longest – step in the human testing process comes in Phase 3 clinical trials, when thousands of people will get candidate vaccines and researchers will see if they are better protected than those who receive only a placebo.
“I’m very impressed that a Phase 3 trial will be started in the United States in late July. That’s a lot faster than I had anticipated based on how long it has taken in the past to get to Phase 3 trials,” said Pamela Bjorkman, a structural biologist at California Institute of Technology.
One big job will be finding volunteers for all the clinical trials. Each vaccine will need to be tested on about 15,000 volunteers while another 15,000 get a placebo. Only then will there be enough power in the analysis to determine the vaccine provides immunity to SARS-CoV-2.
Though more than 138,600 Americans signed up to volunteer on a website launched in late June by the National Institutes of Health, more will be needed. The FDA’s guidance lays out that Phase 3 subjects must include people from the communities hardest hit, especially racial and ethnic minorities and older people.
“I think it’s going to take longer than we might expect” to fill the trials, said Sandra Crouse Quinn, a professor of medicine and senior associate director of the Maryland Center for Health Equity at the University of Maryland.
Erica Ollmann Saphire, a professor at La Jolla Institute for Immunology, worries about how older people, whose immune systems don’t work as well as younger ones’, will respond to a vaccine.
“Will a low dose elicit sufficient protection in elderly people? They typically don’t respond well to some vaccines but are the population we most need to protect,” she said. “If a high dose is needed, will side effects cause people to shy away from use?”
Immunology remains one of the most complex and arcane branches of biology, filled with unknowns and potential pitfalls.
Offit, at Children’s Hospital in Philadelphia, noted the cautionary tale of rotavirus, one of the most common illnesses in infants. First described in the 1940s, it took 50 years to develop a vaccine. In 1999, after 10 months on the market, that vaccine was removed because in very rare cases, it caused intestinal blockages, killing one child. Only in 2006 did a safe rotavirus vaccine make it to market.
In a virus as wily as SARS-CoV-2, “there will be some things we’re going to learn that will be uncomfortable over the next couple of years,” Offit said. “Nature gives its secrets up slowly, grudgingly and invariably with a human costs.”
FDA stance seen as good news
Also new since last month’s predictions was the release June 30 of the Food and Drug Administration’s guidance on how a COVID-19 vaccine should be tested and what would be required for it to be approved for general use.
To win approval, a vaccine must be at least 50% more effective than a placebo in preventing or decreasing the severity of COVID-19.
There had been concern the FDA might face pressure from the White House to lower its standards and approve a COVID-19 vaccine before the Phase 3 trials are done. President Donald Trump has repeatedly promised an approved vaccine by late this year.
The FDA’s actions around a drug called hydroxychloroquine – which it approved under emergency use, then rescinded approval – raised questions about the agency’s independence from the Trump administration. The president strongly supported the drug based on weak early data that has been largely contradicted.
The strong COVID-19 vaccine guidance put some of those concerns to rest, said Peter Pitts, president of the Center for Medicine in the Public Interest. The agency set clear parameters for what “good science” looks like, with solid safety and large effectiveness trials.
“The FDA is saying that it’s not going to be rubber-stamping any vaccines for COVID-19,” he said.
The agency explained how the testing process can be safely streamlined, Nagarkatti said.
“The FDA’s guidance document and Emergency Use Authorization is not trying to cut short safety but to eliminate steps that are time-consuming while sticking to the principle that the benefits should outweigh the risks. This is always the goal of the vaccine,” he said.
Dr. Michelle McMurry-Heath, president and CEO of Biotechnology Innovation Organization (BIO), credited collaborations for the rapid progress: “Our industry is moving forward at an incredibly fast pace, and part of the reason is because of the unprecedented collaboration we’re seeing across the industry and with key government and nongovernmental partners.”
There’s a difference between rushing and expediting, Pitts said.
“Rushing results in mistakes, and that is not an option,” he said. “Expediting means clarifying the pathway (which the FDA has done) and then ensuring that all talent and resources are brought to bear on solid science and savvy regulatory review.”
The guidance will help to rebuild and reinforce the public’s faith in the FDA’s process. That’s especially important when more than a quarter of the U.S. population says it will not get a COVID-19 vaccination, he said.
“This is a crucial public health issue,” Pitts said. “After all, what’s the value of having a vaccine if people don’t use it?”
How we did it
USA TODAY received responses from 14 scientists, researchers and other experts, asking how far they think the vaccine development effort has progressed since Jan. 1, when the virus was first internationally recognized. Those responses were aggregated, and the median was calculated.
This month’s panelists
Pamela Bjorkman, structural biologist at the California Institute of Technology
Kate Elder, senior vaccine policy adviser with the humanitarian group Doctors Without Borders
Sam Halabi, professor of law, University of Missouri, scholar at the O’Neill Institute for National and Global Health Law at Georgetown University.
Florian Krammer, virologist at the Icahn School of Medicine at Mount Sinai in New York City
Dr. Michelle McMurry-Heath, president and CEO of Biotechnology Innovation Organization (BIO)
Dr. Kelly Moore, associate director of immunization education, Immunization Action Coalition; former member of the CDC Advisory Committee on Vaccine Practices; chair, World Health Organization Immunization Practices Advisory Committee
Prakash Nagarkatti, immunologist and vice president for research, University of South Carolina
Dr. Paul Offit, director of the Vaccine Education Center and an attending physician in the Division of Infectious Diseases at Children’s Hospital of Philadelphia
Peter Pitts, president of the Center for Medicine in the Public Interest,
Dr. Greg Poland, director, Mayo Clinic’s Vaccine Research Group, editor-in-chief, Vaccine
Sandra Crouse Quinn, professor of medicine and senior associate director of the Maryland Center for Health Equity at the University of Maryland
Erica Ollmann Saphire, structural biologist and professor at La Jolla Institute for Immunology
Dr. William Schaffner, professor of preventive medicine, Department of Health Policy, and professor of medicine, Division of Infectious Diseases, Vanderbilt University
Prashant Yadav, senior fellow, Center for Global Development, medical supply chain expert
Health and patient safety coverage at USA TODAY is made possible in part by a grant from the Masimo Foundation for Ethics, Innovation and Competition in Healthcare. The Masimo Foundation does not provide editorial input.