Delayed second COVID-19 vaccine dose may not limit efficacy: Studies


Data has continued to accumulate suggesting the UK’s controversial decision to delay the second dose of COVID-19 vaccination may have been a reasonable one. Still, debate does remain over the use of a dosing strategy unsupported by solid clinical trial evidence.

Public Health England has said that early data from the SIREN study “shows a promising impact on infection in healthcare workers aged under 65,” with the first dose of the Pfizer/BioNTech vaccine capable of reducing that risk by more than 70%. The data suggest the vaccine is interrupting virus transmission, rather than just limiting disease severity.

According to PHE: “This data shows clear protection from the first dose, particularly against severe disease, supporting the decision to maximise the number of people vaccinated with a single dose, as advised by the Joint Committee on Vaccination and Immunisation (JCVI).” 

A decision was made in early January to prioritise the breadth rather than the depth of the vaccination rollout, allowing up to 12 weeks between the first and second doses rather than the 3-4 weeks used in the clinical trials leading to the vaccines’ approval.

Objections to this plan focussed largely on the lack of data on the longer interval and on the efficacy of the first dose.

Another study, of the AstraZeneca/Oxford University vaccine, was published in The Lancet in February, involving a pooled analysis of available data from three trials. Overall, the vaccine’s efficacy more than 14 days since the first dose was 66.7%, with 1.0% of more than 8,500 participants testing positive for COVID-19 (compared with 2.9% in a control group).

An exploratory analysis that focussed on day 22 to day 90 following only a single dose showed efficacy of 76.0%, and the analysis suggested protection did not wane over that period. 

In patients who received two standard doses, efficacy was actually higher in those with a longer interval between the doses. The efficacy was 81.3% in those with an interval of at least 12 weeks, compared with 55.1% in those with an interval below six weeks. 

That improvement with a longer interval has not been seen with the other vaccines, and there is still debate over whether the delayed strategy is reasonable. Two experts argued the issue in the New England Journal of Medicine, focusing on the vaccine rollout in the US, where more than 500,000 people have now died of COVID-19 and some have suggested following the UK’s decision to delay the second dose.

“Under normal circumstances, the vaccines should be deployed in keeping with the trial protocols. However, the current circumstances — a slow vaccine rollout, a limited vaccine supply, and the recent emergence of more infectious SARS-CoV-2 variants that threaten to outpace our vaccination program — are anything but normal,” wrote Dr Robert Wachter, of the University of California, San Francisco. “This may be a case in which the risks of strict adherence to the plan outweigh the risks of modifying it.”

Dr Nicole Lurie, also of UCSF, argued that modeling studies suggesting a broader rollout could end the pandemic sooner do not account for the potential degradation of the immune response, or for spillover effects of the decision to delay on vaccine acceptance.

“We don’t even know the duration of immunity produced by the two-dose regimen or how dose timing affects immunity in elderly and immunocompromised persons, who account for most hospitalisations and deaths,” she wrote.

In the UK, opposition to the JCVI’s decision points out other issues in the scientific rationale. “The population risk is that the UK’s delayed second dose could strongly favour the emergence of consequential SARS-CoV-2 variants resulting from sub-optimal or partial immunity,” wrote authors led by Dr John Robertson, of the University of Nottingham, in a letter in The Lancet.

As of 24 February, more than 18 million people in the UK have received the first dose of any of the available vaccines, among the fastest per-capita rollout in large countries around the world. Fewer than 700,000 people had yet received a second dose.

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