Pfizer and BioNTech's experimental coronavirus vaccine works, possibly extremely well.
That's the encouraging conclusion from the companies' announcement Monday of early results from a large clinical trial of some 44,000 volunteers.
After examining 94 cases of COVID-19 in the late-stage study, a data monitoring committee concluded Pfizer and BioNTech's vaccine was more than 90% effective in preventing disease — a better-than-expected outcome and an extraordinary scientific achievement for researchers that 10 months ago were just learning of SARS-CoV-2.
"Everybody is just smiling with delight, knowing what an accomplishment of science this is," said Larry Corey, a virologist at Fred Hutchinson Cancer Research Center and co-head of the National Institutes of Health's COVID-19 Prevention Trials Network.
Beyond the headline, however, Pfizer and BioNTech had little information to share. That's expected, given the monitoring committee only performed its analysis Sunday. The companies said they plan to disclose and publish their data.
"Their outcome is essentially that the vaccine arm was protected from developing disease," said Akiko Iwasaki, an immunologist at Yale University. "That's really all we know now."
For a beleaguered world facing a resurgent pandemic, that's enough right now. But there are many missing details that could matter greatly, not least of which is a detailed look at how safe the shot was for the participants enrolled in the Phase 3 trial.
Earlier, smaller studies have shown vaccination with Pfizer and BioNTech's shot led to side effects like injection site pain, fever, fatigue or chills — most of which were mild or moderate in nature and are typical signs of an immune response to a vaccine. The companies' statement Monday noted no serious adverse reactions had been reported to date.
A fuller reporting will likely come around when Pfizer and BioNTech ask the Food and Drug Administration for an emergency approval, for which the regulator has requested that companies to provide a median of at least two months follow-up for their study participants.
The two-month requirement is meant to capture rarer, more serious side effects that typically emerge between 40 to 60 days after vaccination. Pfizer expects to have those data as early as next week, after which it would formally ask the FDA for an emergency authorization.
Emergency approval is just a first step, made necessary by the urgent need for a coronavirus vaccine. For a full approval of a vaccine, the FDA typically requires at least six months of safety data.
Safety results aren't the only data points scientists and public health officials need to more fully assess Pfizer and BioNTech's vaccine.
Vaccines can be more or less protective due to factors like age or underlying medical conditions. In Pfizer and BioNTech's early studies, for instance, older individuals had somewhat weaker immune responses to vaccination than younger people.
Breakdowns by age from Pfizer's trial, which enrolled individuals older than 12 years, will be critical, as will reporting on whether there were differences between participants who identified as Black, Hispanic or Latino, Asian or Native American.
It's also unclear from the companies' announcement whether the shot is equally protective against mild and more severe COVID-19, or whether vaccination protected against infection as well as disease.
If the vaccine can't block transmission of the virus, prevention guidelines like wearing masks or social distancing will remain critical even after inoculation.
Those questions will only become more important if the vaccine is authorized, and people start to receive the shot outside of the close monitoring of a clinical trial.
"The bottom line is we have much to learn about what's needed to make vaccine policy and to answer the questions that people want about vaccination," Corey said.
Key to any such policy will be information on how long any protective benefit conferred by a vaccine lasts. Pfizer and BioNTech's claim of greater than 90% effectiveness was based on an analysis done one week after the second of two doses. Under a revised plan, the companies will also analyze the vaccine's efficacy at 14 days following the second dose — similar to what other developers' are doing.
Looking further out to months or years post-vaccination, however, "only time can tell whether long-term protection is conferred," said Yale's Iwasaki.
Indeed, at this point, vaccine experts can only guess. Antibodies, the immune cell defenders key to battling foreign pathogens, naturally wane over time, and scientists still aren't certain what levels of antibodies are needed to confer protection in the first place.
"It's always better to have higher efficacy," said Corey, but he added that higher initial effectiveness doesn't necessarily mean longer durability.
Antibodies are only one part of the immune system, which also recruits T cells to fight infection. It's possible that vaccines which readily recruit T cells, as Pfizer's appears to, may be more protective for longer than those that don't.
These lingering questions on durability are why Corey, for one, thinks it is important that coronavirus vaccine trials implement "blinded crossover," in which participants who received a shot get a placebo a year or two later, and vice versa. Doing so would allow researchers to better test how well protection persists.
Pfizer's study, however, is not designed this way, nor does it appear late-stage studies of other leading vaccines are.
More data will come from Pfizer and BioNTech over the coming weeks and months, some of which will hopefully answer the many remaining questions on safety, protective benefit and durability.
For now, however, both Iwasaki and Corey agree Monday's results are very encouraging. "Even though it's very early, it's a great first step," said Iwasaki.