To review the issue: The Oxford/AstraZeneca vaccine uses a modified adenovirus, as do several other vaccines in development, most notably the Russian Gamaleya Institute one. Early, puzzling results suggested that the Oxford vaccine was about 70% effective overall, but that the overall number obscured a disparity between two groups: a two-dose group of all ages that showed efficacy in the 62% range but 90% in a group (including no elderly people) that had received a half-strength dose first. Eh? Even more strangely, the half-dose group seemed to be have given that dose... by mistake? What happened?
Reuters does a deep dive. There's a lot of threads, but it appears that the problem began when the Oxford team didn't trust measurements of the strength of a batch of vaccine from an Italian manufacturer. The Oxford team then measured it using a different technique, concluded it was more potent than the manufacturer said, and trusted its own measurement. Guess who was right? [Time to scream at the void: WHY on earth, given discrepancies between two measurements, both supposedly reliable but using different techniques, WOULD YOU NOT MEASURE AGAIN UNTIL YOU FELT VERY GOOD ABOUT THE DISCREPANCY AND HOW IT HAPPENED?]
"Oxford’s measurement showed that the batch was more potent than the Italian manufacturer had found, the documents show. Oxford trusted its own result and wanted to remain consistent with a measuring tool it had used throughout an earlier trial phase. So it asked Britain’s drugs regulator for permission to reduce the volume of vaccine injected into trial participants from the K.0011 batch. Permission was granted .... The documents published in The Lancet confirm that the error lay with the Oxford researchers. A common emulsifier, polysorbate 80, used in vaccines to facilitate mixing, had interfered with the ultraviolet-light meter that measures the quantity of viral material, according to the documents. As a result, the vaccine’s viral concentration was overstated and Oxford ended up administering half doses of vaccine, believing they were full doses."
This vaccine matters because it is one that developing countries are depending on: it is cheap, and it is stable in refrigerator temperatures, which makes the logistics a lot easier. There is a hypothesis that explains the half-dose/full-dose discrepancy: it's possible that the lower first does primes the immune system better than the higher one; adenovirus variants also circulate in some human populations, and so it's possible that some combination of prior infection and the first dose generated an immune response sufficiently robust that participant's own immune systems destroyed the second dose's virus before it could generate further immune response. The Russians report a 90% efficacy, and that vaccine uses two different adenovirus vectors across the two doses to avoid precisely this risk. These questions need more data, and we're still waiting for the full results of ongoing trials. Adenovirus vaccines matter too: in addition to Oxford, Gamaleya and a Chinese vaccine, the single-dose Johnson & Johnson vaccine, with trial results expected in January, is also adenovirus. In the meantime, Gamaleya is sharing their adenovirus vector, in order to enable a combined trial: one does of the Russian vaccine, and one of the Oxford/Astrazeneca one.
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