The first two coronavirus-vaccine trials ran as smoothly as anyone could hope. And when the results from both Pfizer/BioNTech and Moderna came back with more than 90 percent efficacy, easily surpassing the FDA’s bar of 50 percent, even people like me—who kept telling you to temper your vaccine expectations—reacted with uncharacteristic and unrestrained optimism. These results really were about as good as it gets.
Then came the results for a third vaccine, from AstraZeneca, developed in collaboration with Oxford University. At a glance, these looked good, if not spectacular: an average of 70 percent efficacy. But that top-line result obscured a strange divide between a full, two-shot regimen, which showed 62 percent efficacy, and a half-dose shot followed by a full-dose second shot, which showed 90 percent efficacy. Those split results were immediately confusing—was less vaccine more effective?—but became even more so as more information came to light.
The half dose actually began as a manufacturing mistake, and the volunteers who received it were all younger than 55, and younger people often have better responses to vaccines. Plus, the 90 percent efficacy is based on a small number of cases—possibly small enough to create a statistical fluke. The workings of the human immune system are especially un-intuitive, and scientists have offered plausible biological reasons why a half dose might be superior. But given the data available so far, “it’s basically uninterpretable at this point,” Shane Crotty, an immunologist at the La Jolla Institute for Immunology, says. Several scientists said they were glad that these muddled and confusing results from AstraZeneca/Oxford were not the first COVID-19 vaccine data to be released.