How effective will the COVID-19 vaccines be if the second dose is delayed?

Written by: Rebecca Bridgewater-Gill and Nikki Kendrick

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Following a rapid rise in COVID-19 cases in the UK during December 2020, the Joint Committee on Vaccination and Immunisation (JCVI) advised to prioritise delivery of the first vaccine dose. The aim of this approach was to increase the number of vulnerable people receiving at least the first dose of a vaccine, and hopefully maximise the short-term public health impact of the vaccines.1  Instead of 21 days between doses of the Pfizer/BioNTech vaccine (Comirnaty®) and 28 days for the University of Oxford/AstraZeneca vaccine, an interval of up to 12 weeks (3 months) between vaccine doses is now permitted in the UK.

 

What is known about the effectiveness of this strategy?

 

University of Oxford/AstraZeneca vaccine

Clinical trials of the University of Oxford/AstraZeneca vaccine were originally planned to include some patients who would receive only a single dose.2 However, early analyses showed strong immune responses in people who received a second dose, so everyone in the trial was then offered a booster (second) dose. This change in the planned timings of the vaccinations led to variations in the timings between the two doses (Table). In some cases, people received their second dose more than 12 weeks after receiving the first. Some patients also received a lower dose as their first vaccination.

In these studies, people with longer intervals between the two doses seemed to produce higher levels of antibody* against the SARS-CoV-2 virus,3 suggesting that these people had a stronger immune response to the vaccine (See Figure 1), which could mean greater levels of protection against infection.

 

Figure 1: Antibody levels measured 28 days after the second dose grouped by time between doses3

The vaccine also tended to be more effective if the time between the doses was longer. Overall, in everyone in the trial, the vaccine was 70% effective based on 131 reported cases of COVID-19. This increased to 82% effective in people with more than 11 weeks between doses (see Figure 2).3

However, more than half of people aged 65 years or older had a dose interval of less than 6 weeks.This is important to note because, as people get older, their immune responses tend to get weaker.4  This also means that older people sometimes have a weaker response to a vaccine than younger people. If this was the case in these studies, then this could also explain the observed overall lower antibody levels and effectiveness observed with a shorter dose interval.

 

Figure 2: Effectiveness of University of Oxford / AstraZeneca vaccine by dose interval [3]

There is some information suggesting that a single dose of the University of Oxford/AstraZeneca vaccine may provide immunity for at least 12 weeks (3 months).3 The effectiveness of the vaccine from 22 days after the first dose but before the second dose was given was shown to be 73%, suggesting that a delay in administering the second dose may not affect the protection offered by the vaccine in the short term.

 

Pfizer/BioNTech vaccine

For the Pfizer and BioNTech vaccine, however, there is little evidence to support delaying the second dose. Pfizer and BioNTech have raised concern over the plan to increase the dose interval, stating that:

The safety and efficacy of the vaccine has not been evaluated on different dosing schedules as the majority of trial participants received the second dose within the window specified in the study design. There is no data to demonstrate that protection after the first dose is sustained after 21 days5

The vaccine was estimated to be 52% effective after the first dose but before the second dose.6  However, most cases of COVID-19 in vaccinated people happened soon after the first dose. When the effectiveness of the vaccine was calculated from 15 days after the first dose but before the second dose was given, the vaccine was estimated to be 89% effective,1 compared with 95% effective from 7 days after the second dose.6  However, it is unclear how long the protection from the first dose would continue without a second dose.

 

*Antibodies are found in the blood and are one of the ways that the body can fight off an infection.

 

References
  1. Joint Committee on Vaccination and Immunisation, “Optimising the COVID-19 vaccination programme for maximum short-term impact,” 6 January 2021. Available at: https://www.gov.uk/government/publications/prioritising-the-first-covid-19-vaccine-dose-jcvi-statement/optimising-the-covid-19-vaccination-programme-for-maximum-short-term-impact [Accessed January 2021].
  2. Voysey M, Clemens SAC, Madhi SA, et al. “Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK,” Lancet 2021;397:99–111.
  3. Medicines & Healthcare products Regulatory Agency, “Public Assessment Report Authorisation for Temporary Supply: COVID-19 Vaccine AstraZeneca, solution for injection in multidose container COVID-19 Vaccine (ChAdOx1-S [recombinant]),” 2020.
  4. Lang PO, Govind S, Michel JP, et al. “Immunosenescence: Implications for vaccination programmes in adults,” Maturitas 2011;68:322–330.
  5. Reuters, “BioNTech says no data to support delayed vaccine booster shot,” 4 January 2021. Available at: https://www.reuters.com/article/idUSKBN2991XX [Accessed January 2021].
  6. Polack FP, Thomas SJ, Kitchin N, et al. “Safety and Efficacy of the BNT162b2 mRNA,” N Engl J Med 2020;383:2603–2615.

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