Despite a rocky start, AstraZeneca tosses its hat into the COVID vaccine ring

Written by: Parker Davis
Edited by: Esther Melamed

In addition to Pfizer/BioNTech announcing their vaccine as being up to 95% effective in Phase 3 trials, Moderna and the University of Oxford partnered with AstraZeneca have added their names to the list of published vaccine efficacy data. Astonishingly, Moderna has reported in a news update that its vaccine is about 94% effective in preventing COVID-19, and recent reports indicate that not a single volunteer in their trial developed severe symptoms (Cohen, 2020). What’s more, early data from Phase 1 and 2 trials indicate that these vaccines may produce robust efficacy in preventing COVID-19 across a wide swath of age ranges. It is important to keep in mind, however, that not all of this data has been peer-reviewed, so we will need to remain vigilant as more of it is released. As of December 1, 2020, both Pfizer and Moderna have submitted their candidates to the FDA for Emergency Use Authorization.

In an initial press release on November 23, AstraZeneca announced the results of their Phase 3 trials which indicated an approximately 70% prevention rate for their vaccine. Though not as efficacious as the mRNA vaccines, these results were still lauded for their unprecedented rapidity. However, this figure of 70% is closer to an average or a conflation of the results of two distinct dosing regimens that the company ran inadvertently. In the trial, a fraction (n = 2,741, roughly one-third) of all participants received a half-dose of the vaccine due to what AstraZeneca referred to as a “serendipitous miscalculation”. Once the mistake was recognized, these individuals received the full-dose one month later, as predetermined by the parameters of the trial. In this cohort, the vaccine actually proved more efficacious – approximately 90% – than in the cohort that received two full doses (hence the serendipity). These findings left the scientific community understandably puzzled. Possible theories as to why these results may be the case have been proffered: Katie Ewer, who worked on the vaccine, says that it is possible the lower dose may have stimulated the T cell response more strongly, providing better support for antibody production; another explanation is that our reaction to the chimpanzee adenovirus vector may have “blunted” the response to the viral antigen itself. One piece to consider is that the more effective half-dose cohort was composed of fewer individuals with a lower average age than the full-dose cohort, which could have played a more significant role in confounding the results than we realize. These are just theories. In truth, nobody is quite certain why these data came to be, or what they may tell us about our immune functions. But one thing is certain: as the consuming public, we have the right and the responsibility to ask questions and ensure that these data stand up to intense scrutiny. Optimistically, however, nobody who received this vaccine developed severe symptoms of COVID-19. And results from this trial may indicate that the vaccine prevents transmission of the virus by asymptomatic individuals (Callaway, 2020).

Now that a vaccine for COVID-19 has resolved from the abstract to the concrete, an important metric to consider will be the distribution of and widespread adherence to vaccination. In the clinical trials for all three vaccine candidates described above, no serious adverse reactions were reported. Researchers estimate that fewer than 2% of individuals who received the mRNA vaccines from Moderna and Pfizer experienced symptoms that limited daily activity. While this is exciting news, both companies have reported that some of the more mild, transient reactions – such as sore arms, fevers, mild nausea, etc. – occurred at higher rates than for normal influenza vaccines (Wadman, 2020). Public health officials worry that this may dissuade people from coming back for the necessary second dose or from receiving any vaccination in the first place. This high rate of reaction means that communication by the scientific and public health communities will be key for quelling distrust and unwillingness to vaccinate.