After months of safety trials, large-scale clinical testing is finally getting underway for the leading novel coronavirus vaccine candidates.
The Trump administration hopes to approve at least one vaccine for widespread use before the end of the year. However, many experts are skeptical that a vaccine will be ready that quickly. And even when a vaccine is ready, actually deploying it could be easier said than done.
With or without a vaccine, America is in for a long, difficult fight against a stubborn and deadly virus that, as of Friday, had infected nearly 2.8 million Americans and killed more than 129,000, according to Johns Hopkin’s coronavirus tracker.
There are no fewer than 155 SARS-CoV-2 vaccine candidates in development all over the world, according to The New York Times. Just one, the product of a crash Chinese program, is in limited use—and only in the Chinese military.
The U.S. government has picked five mainstream vaccine candidates for serious federal support. The feds’ Operation Warp Speed, as it’s been dubbed, has tapped Moderna; a consortium of AstraZeneca and Oxford University; Johnson & Johnson; Merck; and Pfizer to receive $13 billion in government funding.
AstraZeneca and Oxford have already begun large-scale, phase three trials in the United Kingdom, Brazil, and South Africa. Moderna began phase three trials this week in the United States. Johnson & Johnson plans to begin its own large-scale trials later this month. Several of the leading pharmas have already begun manufacturing doses in the hope of having sizable stockpiles if and when the FDA approves their vaccines.
Officially, the goal is to produce 300 million doses of a vaccine by January 2021. Anthony Fauci, the head of the National Institute for Allergy and Infectious Diseases, stressed that the January goal is “aspirational, but it’s certainly do-able.”
Even then, it could take months to vaccinate a significant portion of the U.S. population, assuming there are no major complications in the manufacturing and distribution of doses and supporting materials such as vials.
There are some major differences between the five federally supported vaccine candidates that could weigh on their trials and, in the event they receive government approval for widespread use, their effectiveness in the public.
Moderna’s vaccine candidate, like Pfizer’s, is an mRNA vaccine that includes a synthetic version of the messenger-RNA that a virus uses to build its infectious proteins. Meanwhile, Johnson & Johnson and the AstraZeneca-Oxford consortium are working with so-called “live-vector vaccines” that include inactive versions of the novel coronavirus.
Even if all five vaccine candidates complete development and the Food and Drug Administration approves each for public use, there still could be big differences in their effectiveness. “It is not clear where the active immunities resulting from different vaccines will be exactly the same,” Dmitry Korkin, a bioinformatics researcher at the Worcester Polytechnic Institute in Massachusetts, told The Daily Beast.
The mRNA vaccine candidates that Moderna and Pfizer are developing are perhaps the riskiest, as they’re also the newest. “There’s never been an mRNA vaccine that’s been successfully produced and marketed,” Jeffrey Klausner, a professor of medicine and public health at UCLA who previously worked at the Centers for Disease Control, told The Daily Beast. “Anything new is going to definitely take longer and be rigorously assessed.”
“The mRNA vaccines are novel and only time will tell what the risks will be,” Lola Eniola-Adefeso, a University of Michigan bio-engineer, told The Daily Beast.
One problem with mRNA vaccines is that scientists aren’t even sure what to look for in order to judge how effective a vaccine might be in the early stages of a potential infection. “Different types of vaccines produce different antibody types and can produce different cellular responses,” Klausner explained. “In intermediate-phase trials, the kinds of markers of efficacy are well-known for some types of vaccines but less known for newer types.”
The more old-fashioned candidates, such as the live-vector vaccines that Johnson & Johnson and the AstraZeneca-Oxford consortium are working on, could move more smoothly through development. Neither Moderna nor Johnson & Johnson responded to a request for comment.
Where an mRNA vaccine is entirely synthetic, pharmas produce live-vector vaccines using samples of the virus they’ve extracted from patients. Lab techs inactivate the virus by exposing it to heat before adding it to the vaccine. This is the same process that the pharmaceutical industry uses for many of the annual flu vaccines.
But there’s a catch. If development of a novel coronavirus vaccine ends up following the same general model as flu vaccines, it could produce a vaccine that works, but doesn’t work perfectly—and doesn’t last very long. The flu virus evolves quickly, requiring constant updates to vaccines and annual immunization for the best protection.
“Americans are counting on a [coronavirus] vaccine that you only have to get once or twice that will provide long-term protection,” Jennifer Reich, a University of Colorado sociologist who studies immunization, told The Daily Beast.
“If the vaccine works more like a flu vaccine, which provides annual protection and may not entirely eliminate the risk of infection but dramatically reduces the risk of death, people will view it differently than other vaccines for which one or two inoculations provides lifetime protection,” Reich explained.
The more frequently people must get vaccinated and the weaker the protections resulting from any one immunization, the less faith people are likely to have in a particular vaccine—and the less likely they are to line up at their local pharmacy for a shot.
That could have serious implications as U.S. authorities try to immunize enough people to provide population-wide protection against major outbreaks of COVID-19. “Most people think about vaccines as a question of personal benefit and individual risk,” Reich said. “Yet vaccines are also most effective when high proportions of the population use them.”
No one knows yet how effective an mRNA vaccine might be or what its deployment strategy might look like. But if an mRNA vaccine confers greater immunity in fewer doses, it could help to solve the problem with vaccines in the vein of today’s flu vaccines—weak protection that requires frequent re-immunization.
Which is to say, it matters which companies win the race to develop effective novel-coronavirus vaccines. And it might help if they all win, resulting in a wide array of vaccines, each with its own production lines, effectiveness, and duration of immunity.
Paul Offit, chief of the division of infectious diseases at the Children's Hospital of Philadelphia, told The Daily Beast he thinks there will be more than one vaccine for SARS-CoV-2. But he cautioned against declaring victory too quickly, even after the first couple vaccines hit the streets.
Sometimes the FDA approves vaccines that, while safe, work better in experimental settings than they do in the messy world of the general public, Offit explained. “Never breathe a sigh of relief until the first three million doses are out there.”