COVID-19 Vaccine Efficacy After First Dose: Pfizer, Moderna, AstraZeneca

Photo taken in Bucharest, Romania
New data about Pfizer COVID-19 efficacy after the first dose suggests high efficacy, raising questions about potential alternative dosing schedules.


In a letter to the editor published in The New England Journal of Medicine, Danuta M. Skowronski, MD, and Gaston De Serres, MD, PhD, reviewed documentation submitted to the Food and Drug Administration to derive vaccine efficacy for Pfizer’s COVID-19 vaccine, BNT162b2.1 In the original study, conducted by Polack et al, efficacy after the first dose was calculated to be 52.4% and collected during the first 2 weeks after injection, when “immunity would have still been mounting.”1,2

Their analysis concludes that prior to the second dose, BNT162b2 has an efficacy of 92.6%.

Dr Skowronski and Dr De Serres go on to recommend that “With such a highly protective first dose, the benefits derived from a scarce supply of vaccine could be maximized by deferring second doses until all priority group members are offered at least one dose.”

There is limited data on an alternative vaccine schedule and duration of protection after the first dose. However, correspondence authors state that given the current vaccine shortage, following the current vaccine schedule provides little short-term benefit.

Pfizer’s response to the authors emphasizes the lack of data surrounding alternative dosing regimens. “The decision to implement alternative dosing regimens resides with health authors,” they state. Pfizer’s representatives reiterate the importance of conducting surveillance on implemented alternative dosing schedules to ensure vaccines provide the most optimal protection.


The analysis of Pfizer’s first-dose efficacy is similar to the Moderna COVID-19 vaccine, mRNA-1273, which was reported to be 92.1% in an FDA briefing document, published on December 17, 2020.3


Results from 3 single-blind, randomized controlled trials in the United Kingdom, Brazil, and South Africa indicated that a 3-month dose interval might have advantages over a short-dose interval.4 This change serves 2 purposes: to vaccinate the largest population when supplies are scarce and to improve protection after the second dose.

An exploratory analysis showed that vaccine efficacy against primary symptomatic COVID-19 was 55.1% (95% CI, 33.0-69.9%) with an interval of less than 6 weeks and 81.3% (95% CI, 60.3-91.2%) with an interval of at least 12 weeks.

Efficacy against asymptomatic infections in the United Kingdom showed similar results, with increased efficacy correlated with increased intervals.

A single standard dose of the vaccine was shown to maintain 76% efficacy (95% CI, 59.3-85.9%) against primary symptomatic COVID-19 in the first 3 months after vaccination. However, it does not protect against asymptomatic infection over the same time period (vaccine efficacy, -17.2%; 95% CI, -248.6 to 60.6%). A single dose did exhibit protection against any nucleic acid amplification test-positive infection from 22 to 90 days.

“Vaccination programs aimed at vaccinating a large proportion of the population with a single dose, with a second dose given after a 3-month period, might be an effective strategy for reducing disease,” the study authors concluded.


1. Skowronski DM, De Serres G. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. Letter. N Engl J Med. Published online February 17, 2021. doi:10.1056/NEJMc2036242

2. Polack FP, Thomas SJ, Kitchin N, et al; for the C4591001 Clinical Trial Group. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N Engl J Med. Published online December 31, 2020. doi:10.1056/NEJMoa2034577

3. Vaccine and Related Biological Products Advisory Committee Meeting FDA briefing document: Moderna COVID-19 vaccine. December 17, 2020. Accessed February 23, 2021.

4. Voysey M, Clemens SAC, Madhi SA, et al; on behalf of the Oxford COVID Vaccine Trial Group. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. Lancet. Published online February 19, 2021. doi:10.1016/S0140-6736(21)00432-3