The UK's chief medicial officers - faced with the increased threat from the more transmissible variant and a health service under pressure - now recommend that the gap between the first and second vaccine doses should be lengthened to allow more people to receive the first dose and therefore a certain level of protection. It says a second dose of the vaccine can be administered within 12 weeks.
The US, in contrast, has stated that it will not make any changes to the 21 day spacing between doses. Denmark is allowing up to six weeks between doses, as is France.
The WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) puts the maximum delay between doses at six weeks: given that clinical data is available for up to 42 days between doses.
2nd dose delay acceptable 'for a few weeks'
The committee notes the difficulties countries may face in rolling out limited doses of vaccine and their eagerness to vaccinate as many people as possible when faced with increasing case numbers.
“SAGE recommend the administration of two doses of this [Pfizer/BioNTech] vaccine within 21 to 28 days,” said Dr Alejandro Cravioto, SAGE chair, at a press briefing this week.
“While we acknowledge the absence of data on safety and efficacy after one dose beyond the three/four week studied in the clinical trials, SAGE made a provision for countries in exceptional circumstances of vaccine supply constraints and epidemiologic settings to delay the administration of the second dose for a few weeks in order to maximise the number of individuals benefiting from a first dose.”
While it recommends the maximum delay between doses should be six weeks, the SAGE committee also says that an individual who has had a delay in getting the second dose – for whatever reason – can still receive a second dose: “There’s no outside limit at which point we say ‘you can’t get your second dose’.”
The UK says the 2nd dose of authorized COVID-19 vaccines - whether Pfizer/BioNTech or AstraZeneca - should be administered within 12 weeks.
This poses less of an issue with the AstraZeneca vaccine - clincial trials did look at longer delays between doses - but the majority of participants in the Pfizer/BioNTech trials were given the second dose after a set 21 days (a small number of participants received the 2nd dose up to 42 days later).
Responding specifically to the UK’s strategy of spacing out doses, Dr Kate O’Brien, Director, Immunisation, Vaccines and Biologicals at the WHO, says each country is weighing the risks and rewards of the strategy in the context of their own situation.
“I think everybody realises that we're operating in a space where the amount of evidence to drive policy decisions is evidence that is evolving.
"What many communities are doing is weighing the evidence that we do have about the efficacy and the immunogeneicity that has [been] derived from clinical trials where the timing of doses is delivered in a specified timing, against what to do around the possibility and some evidence that shows the possibility that single-dose efficacy between the timing of the first and the second dose is quite high."
Countries with constrained supply have to consider how they give out the first doses of the vaccine in the context of how supply is rolling in; weigh up broader rollout of a first dose against a second dose delay; and whether they want to risk administering the vaccine outside the parameters of clinical trials without evidence for efficacy;
"What we're seeing around the world is different committees are weighing those risks and discussing those risks in different ways.”
WHO recommendations for pregnant women and people who have already had COVID-19
The SAGE committee met on Tuesday (Jan 5) to consider the Pfizer/BioNTech vaccine. Alongside the issue of a delay between doses, it has also made the following recommendations with regards to giving the vaccine to pregnant women, people who have already had COVID-19, and future research priorities
Pregnant women: “In the light of the data limitations SAGE was not able to provide a recommendation for the use of the vaccine in pregnancy until more safety data are available. However we made a provision for situations where the benefit of vaccination of a pregnant woman outweighs the potential risks, such as health workers at high risk of exposure. We have done this before for other vaccines, as the use of the Ebola vaccine in the Democratic Republic of Congo before.”
People who have already had COVID-19: “SAGE recommends that COVID vaccination be offered regardless of a person's history of asymptomatic or symptomatic SARS-Co2 infection. Available data currently indicate that symptomatic reinfection within six months after an initial infection is rare. Thus in the context of limited vaccine supply persons with a PCR-documented SARS-CoV2 infection in the preceding six months may choose to delay vaccination until near the end of this time period.
“This would encourage the use of the vaccines for other people who have not been exposed to the virus and thus have a much larger portion of the population protected.”
Future research priorities: The SAGE committee notes continued collection of data for authorized vaccines as roll-outs continue. It sets the priority for vaccine research as assessing vaccines’ efficacy against SARS-CoV transmission, the duration of protection, vaccine efficacy against the virus variants (particularly in light of new variants emerging from South Africa and the UK), and vaccine efficacy and safety in children younger than 16 years old.
It also notes the need to prioritize research on the immunogeneicity and safety and especially cotransmission with other vaccines and vaccine interchangeability. “This is important especially with the co-administration for the elderly group with an influenza vaccine if that were possible.”