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1/ Should we give as many people one dose of the Pfizer and Moderna vaccines as possible? Or half as many people two doses of vaccine? It’s a data-free zone. https://twitter.com/CitizenCohn/status/1358075667573862401
2/ Here’s the Pfizer COVID vaccine clinical trial data. Study participants got their 2nd dose at 21 days. We only have data on how well one dose of the Pfizer vaccine was at protecting against COVID during that 21 day / 3 week period after the first dose. https://www.nejm.org/doi/full/10.1056/NEJMoa2034577
3/ We don’t know how good or how long that protection would last if someone did NOT get that 2nd dose at 21 days.
4/ Here’s the Moderna COVID vaccine clinical trial data. Study participants got 2nd dose after 28 days. So we only have data on how well one dose of the Moderna vaccine was at protecting against COVID during that 28 day / 4 week period after the 1st dose. https://www.nejm.org/doi/full/10.1056/NEJMoa2035389
5/ We don’t know how good or how long that protection would last if someone did not get that 2nd dose of Moderna vaccine at 28 days.
6/ We can’t extrapolate protection during that 21-/28-day period between doses to what would happen if someone did NOT get a 2nd dose until months later (or at all). We can make educated guesses, but that's hypothesis and conjecture, not science.
7/ Here’s the data on neutralizing antibody titers in study participants receiving the Pfizer vaccine. Note that the titers are much lower after one dose (measured just prior to 2nd dose at 21 days) than after two doses (measured at 28 and 35 days). https://www.nejm.org/doi/full/10.1056/NEJMoa2027906
8/ Here’s the data on neutralization antibody titers in study participants receiving the Moderna vaccine. Note that the titers are much lower after one dose (measured just prior to 2nd dose on day 29 of the study) than after 2 doses (measured at 43 days). https://www.nejm.org/doi/full/10.1056/NEJMoa2028436
9/ Here’s data on CD4+ T-cell responses among study participants receiving the Moderna vaccine. https://www.nejm.org/doi/suppl/10.1056/NEJMoa2028436/suppl_file/nejmoa2028436_appendix.pdf
10/ Note that T-cell activity was significantly lower after one dose (measured just prior to second dose on day 29 of the study, 28 days after the first dose) than after two doses (measured at 43 days).
11/ The second doses of the Pfizer and Moderna induced higher levels of antibodies and T-cell responses than one dose alone. T-cells are important in generating immunologic memory. The second dose of both vaccines seem to be important in generating stronger and durable immunity.
12/ The CDC has said patients can wait up to 6 weeks between doses. I (& others like @DrPaulOffit) think that’s OK, but I wouldn’t wait much longer than that. The strength of the immune response is weaker after only one dose & we don't know how durable. https://www.chop.edu/centers-programs/vaccine-education-center/video/protecting-the-public-with-limited-covid-19-vaccine-supply-1-or-2-doses
13/ Is it possible that delaying the 2nd dose more than 6 weeks could result in greater durability of response? Based on data from the AstraZeneca trial & on the Chinese Sinovac Biotech vaccine, yes. But whether that applies to the Pfizer & Moderna vaccines, we don't know.
14/ There are many things we'd like to know. But we need to design studies and test our hypotheses. Now is the time to do this (like @peterbachmd has argued), before many have been vaccinated and while there's still widespread community transmission. https://www.statnews.com/2021/01/04/stop-debating-first-shot-vs-set-aside-hospitals-should-compare-them/
15/ We should test different dosing schedules, with longer intervals between doses. We should test hybrid regimens that combine different types of vaccines, like Oxford is doing, alternating doses of the AstraZeneca and Pfizer vaccines. https://www.abc.net.au/news/2021-02-04/oxford-university-announces-trial-alternating-covid-19-vaccines/13123422
16/ And we should monitor carefully whether lower neutralizing antibody activity could create immune pressure for more mutation to occur and more variants to emerge. There could be a very real risk to generating partial, not complete immunity.
17/ This, too, is a hypothesis and needs to be studied.
