With millions of lives on the line, researchers have been working at an unprecedented pace to develop a COVID-19 vaccine.
But that speed _ and some widely touted breakthroughs _ belie the enormous complexity and potential risks involved. Researchers have an incomplete understanding of the coronavirus and are using technology that's largely unproven.
Among many worries: A handful of studies on COVID-19 survivors suggest that antibodies _ key immune system proteins that fight infection _ begin to disappear within months. That's led scientists to worry that the protection provided by vaccines could fade quickly as well. Some even question whether vaccines will really end the pandemic. If vaccines produce limited protection against infection, experts note, people will need to continue wearing masks and social distancing even after vaccines roll out.
Yet in an interview with KHN, the country's top infectious disease expert, Dr. Anthony Fauci, said he's "cautiously optimistic" that researchers will overcome such obstacles.
"We know the body can make an adequate response against this virus" after two shots of a vaccine being tested, Fauci said. "There's no reason to believe that we won't be able to develop a vaccine against it."
Because early-stage trials began just a few months ago, doctors don't know how long antibodies in vaccinated people will last, he said.
Scientists will get answers to some of their questions from the country's first large-scale COVID-19 vaccine trial, launched last week by the National Institutes of Health and Moderna at 89 locations around the country.
"Once we get a protective response, we will see how long it lasts," Fauci said.
"If we don't get as long a response as we want, we can always give a booster shot."
The leading vaccine candidates are based on new approaches that have never resulted in a licensed vaccine. Moderna, a relatively young company, has yet to produce any approved vaccines.
"Even more so than usual, as we create vaccines, we're sailing in uncharted water," said Dr. William Schaffner, a professor at the Vanderbilt University School of Medicine.
If approved, a COVID-19 vaccine created by researchers at Oxford University and drugmaker AstraZeneca would be the first licensed vaccine to use a virus that causes colds in chimpanzees but doesn't sicken people. Scientists use the cold virus to deliver key elements of the vaccine into a patient's body. In this case, the virus delivers the gene that instructs the cell to make the spike protein, which helps the novel coronavirus enter cells.
Early studies show that the Oxford vaccine stimulates the immune system as intended. If the vaccine is successful, these antibodies and other immune cells will recognize and neutralize the spike protein if they encounter it again, protecting people from disease.
Two other candidates _ a vaccine from Moderna and another from Pfizer and BioNTech, a German company _ were also developed with novel methods. They use genetic material from the coronavirus called messenger RNA, or mRNA.
Unlike traditional vaccines, which expose the body to a viral protein to stimulate the immune system, mRNA acts as an instruction kit, telling the body how to construct the proteins itself. The immune system then responds to the viral protein by making antibodies.
Moderna officials have said they were able to produce the COVID-19 vaccine so rapidly because they had developed experimental vaccines against two other lethal coronaviruses _ those that cause SARS and MERS _ which are closely related to the COVID-19 virus.
When the pandemic emerged, Moderna tweaked those vaccines to target COVID-19, Fauci told KHN. Fauci's team contacted the company the day after China made the virus's genome public.
Two months later, Moderna's vaccine was ready for a trial because "98% of the scientific work had been done," Schaffner said. "They went back to these scientific methods and adapted them very quickly. That saves years of work."
But there is a potential risk in relying so heavily on unproven techniques: New technology can sometimes cause unforeseen problems or side effects, said Dr. Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security.
For all their differences, most of the vaccines in development target the spike protein, Adalja said. That is likely a winning strategy, considering successful veterinary coronavirus vaccines also target the spike protein.
But some scientists say this uniform approach could also leave us vulnerable.
Ideally, scientists should diversify the portfolio of vaccines, in case targeting the spike protein doesn't work as well as researchers hope, Adalja said. Developing a vaccine that targets other key proteins might help scientists to hedge their bets.
Researchers around the world are working on more than 165 vaccines; more than two dozen are already being tested in people. Early human studies focus on safety and finding the best dose. Later clinical trials are larger and measure a vaccine's effectiveness by comparing the outcomes of volunteers who receive the vaccine with those of people given a placebo.
Fauci said he's reassured by early studies that showed the Moderna vaccine to be safe. Although some volunteers developed fevers and headaches after vaccination, these side effects were no worse than those caused by other licensed vaccines.
"That's not a showstopper at all," he said.
