A: The Oxford/Astrazeneca vaccine was granted emergency authorization & the British government has decided to give as many people a first vaccine dose while delaying second doses *up to* 12 weeks after the first.
A big news week here in the UK where this Nerdy Girl (Jenn) lives. Besides the worldwide focus on the new mutant “UK variant”, the homegrown Oxford vaccine was approved, and a somewhat surprising vaccine deployment strategy was announced.
See our previous post for a run-down on the Phase III trial results thus far from Oxford/Astrazeneca- Phase III trials in the US are still underway.
TL;DR on the Oxford Vaccine:
⬆️PRO: compared to mRNA vaccines, cheaper and requires only normal refrigeration.
⬆️PRO: No cases of severe disease were seen in the vaccine group
⬇️CON: trial efficacy for two standard doses was 62% compared to 95% for Pfizer & Moderna
⬇️CON: More efficacious lower first dose strategy (90%) only given to small group & needs to be verified in larger trial.
🙋 What is with this maverick “one dose” strategy? Does this make any sense?
Basically, because cases are rising very quickly in the UK (possibly due to increased transmissibility of the new variant) and hospitals are under tremendous pressure, there is an urgent need to get vaccines deployed as quickly as possible.
The UK is trialing an approach to get more people a first dose as soon as possible, while *delaying* (but not foregoing) second doses. The logic of the approach is that dramatically increasing the number of people given at least partial protection quickly will prevent more hospitalizations and deaths than vaccinating fewer people with two doses in the same amount of time.
This approach reflects a classic tension between strategies that may be best for the population versus the individual. While each individual will be better off with two full doses (see our recent post on prime-boost, society as a whole may benefit from fewer severe illnesses and deaths if more people have partial protection sooner.
🤔 Sounds reasonable. What are the downsides?
⌛ WANING IMMUNITY. While the trial data look good after one dose, we don’t know the length of that immunity and immunologists emphasize the second dose is still crucial for full protection. Efficacy after the first dose of the Pfizer vaccine (measured from 14 days) was 89%, but the length of that protection is unknown since everyone in the trial got a second dose after three weeks. Similar first dose protection was found for the Moderna mRNA vaccine.
The Oxford/Astrazeneca vaccine had different lengths of time between doses as part of the trial. 62% of the participants had at least 6 weeks between doses. Protection from severe disease was high after a single dose. There was evidence that a longer interval between the first and second doses promotes a stronger immune response with the AstraZeneca vaccine. The regulatory agency (MHRA) thus recommended that the second dose be administered between 4 and 12 weeks after the first dose.
The UK is planning to delay second doses for *both* the Pfizer and Oxford/Astrazeneca vaccines, causing Pfizer to issue a warning that they cannot ensure efficacy if their protocol is changed.
🦠 VIRAL ADAPTATION. Another concern is that with very high levels of transmission and only partial immune protection, this may be a recipe for the virus to evolve resistance to the vaccine. This could happen if rather than hammering the virus quickly with the full immune response, partial vaccination allows the virus to still replicate in someone’s body even if it prevents severe illness. Any mutations from this replication that evade the vaccine-induced immunity would be more likely to survive and get passed on.
😈 BEHAVIOR CHANGE: We’re all super anxious to get back to normal life. People who receive a first dose may feel freer to take more risks despite not having full protection, leading to more transmission. Longer gaps between doses may make it less likely that people will return for their second dose.
👇 SUMMARY:
💥 In this time of exponential case growth, vaccinating double the numbers with slightly less efficacy may prevent more hospitalizations and deaths than half the vaccinations with full 95% efficacy.
💥 This assumes there isn’t significant decline in immunity several weeks after first dose, or that later dosing will not reduce overall efficacy.
This strategy is a gamble, as we don’t know for certainty the answers to the key questions above. Slower deployment of the two-dose protocol has its own trade-offs. Policymakers are having to make difficult decisions under uncertainty with many, many lives at stake.
Dr. Anthony Fauci mentioned yesterday that the U.S. is considering altering current protocols to increase the number of Americans inoculated, but the specifics of these discussions are not known.
These are tough scientific and policy decisions, which the Nerdy Girls are following and discussing intensely amongst themselves. We strive to keep you as up to date on the state of the science as we can. Stay safe and….. Stay tuned!
Love,
The Nerdy Girls
Further reading:
“U.K. Authorizes Covid-19 Vaccine From Oxford and AstraZeneca”
Tweet thread on one vs. two dose strategy from immunologist Dr. Akiko Iwasaki
