- Jennifer Middleton, MD, MPH
Last month, I wrote about the process for vaccine approval by the United States (US) Food and Drug Administration (FDA). Since then, the Pfizer/BioNTech SARS-CoV-2 vaccine has received Emergency Use Authorization (EUA), joined by the National Institutes of Health (NIH)/Moderna vaccine at the end of last week. These two vaccines use a novel mRNA process to induce immunity; a third vaccine by Oxford/AstraZeneca, which instead uses a chimpanzee adenovirus vector ("viral vector"), has just published its interim analysis data.
The Oxford/AstraZeneca ChAdOx1 vaccine was tested in nearly 35,000 individuals across Brazil, the United Kingdom (UK), and South Africa in phase 2/3 trials. Importantly, only adults aged 18-55 were enrolled. When researchers received the manufactured vaccine in the UK, though, their measurement of the viral particle concentration was higher than expected. To maximize safety while their teams resolved this discrepancy, they chose to inoculate the first group of participants with a lower dose for their first injection. Once the researchers settled the issue with their quantification methods, all participants then received the originally planned full dose of the vaccine for their second injection. Later UK enrollees and participants at the other trial sites received the full dose for both injections.
Interestingly, the low dose cohort had better protection against COVID-19 than the participants who received two full dose injections:
In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; p=0·010).
The researchers did not have an explanation for this surprising finding, though they rightly point out that the confidence intervals are quite wide for both values.
This vaccine is unlikely to achieve EUA status in the US soon. Oxford/AstraZeneca failed to promptly notify the FDA of the dosing snafu as well as the decision to pause trials in September after a participant was diagnosed with transverse myelitis. The FDA reportedly learned about these issues via the lay press and not the study investigators, which reportedly did not sit well with FDA leadership. The FDA didn't clear Oxford/AstraZeneca to resume vaccine trials in US until October, which put them behind Pfizer/BioNTech and NIH/Moderna in the race to generate phase 3 trial data. And, they have yet to produce any data regarding their vaccine's efficacy in adults over the age of 55, the population arguably at greatest risk of COVID-19 mortality.
Assuming it eventually catches up, the Oxford/AstraZeneca vaccine has several appealing properties. Unlike the two mRNA vaccines by Pfizer/BioNTech and NIH/Moderna, the Oxford vaccine does not require ultra-cold storage and is much less expensive to produce. For parts of the world where storing and/or procuring an mRNA vaccine is not affordable or practical, the Oxford/AstraZeneca vaccine offers an alternative.
The AAFP held a virtual town hall last week about the COVID-19 vaccines, and the Centers for Disease Control and Prevention (CDC) has also outlined its allocation recommendations for the initially limited supply of vaccine. We'll also continue to update the AFP By Topic on Coronavirus Disease 2019 (COVID-19).