In the Journals: The Importance of Two Doses of COVID-19 mRNA Vaccines

In December 2020, two mRNA vaccines to prevent COVID-19 were approved for use by the Food and Drug Administration (FDA). Both vaccines are given as a series of two doses with the second dose following either three weeks (Pfizer) or four weeks (Moderna) after the first.

Unfortunately, both mRNA vaccines are currently in short supply. In response, the CDC has issued guidelines for how to deal with this problem. The CDC stated that under “exceptional circumstances,” where the current recommendations for dosing can’t be met, the second dose can be given six weeks after the first dose. The CDC reasoned that recipients would still get the booster response from the second dose, even if it was given a few weeks beyond the way in which the vaccines were studied.

On Feb. 17, 2021, The New England Journal of Medicine published a letter to the editor from two Canadian researchers that re-evaluated the impact of one dose of Pfizer’s mRNA vaccine (Skowronksi D. & De Serres G. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020 Dec 31;383(27):2603-2615). The researchers evaluated vaccine efficacy between the first and second dose of the Pfizer vaccine in protection against COVID. They found that the efficacy after dose one and before dose two was 52.4%. The efficacy seven days after dose one to before dose two was 68.5%. And the efficacy 14 days after dose one to before dose two was 92.6%. Because everyone who participated in the Pfizer trial received a second dose, the efficacy of one dose of vaccine could not be evaluated for longer than a few weeks.

Unfortunately, the media carried this analysis as a “new study” showing that one dose of Pfizer’s vaccine was as effective as two, which isn’t true. This letter was the opinion of two scientists; unfortunately, it overlooked important immunological and evolutionary considerations. First, during phase I studies, a second dose of Pfizer’s vaccine induced a vigorous booster response as shown by both a dramatic rise in the level of virus-specific neutralizing antibodies as well as the detection of both helper T cells and cytotoxic T cells. The detection of T cell responses presaged longer-lasting immunity than that found after a single dose. Second, a lower neutralizing antibody response following a single dose might inadvertently increase the generation of viral variants by decreasing protection against infection.

The Pfizer and Moderna vaccines are both two-dose products. The choice to get only a single dose would likely result in an under-immunized population with short-term protection.