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0222 PHE real-world Comirnaty
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U.K. adds to real-world data backing flexible COVID vaccine schedule

Feb 23, 2021 | 2:07 AM GMT

Public Health England has bolstered the U.K.’s case for flexible vaccine dose schedules with its analysis of real-world data from healthcare workers and elderly people immunized with Pfizer and BioNTech’s Comirnaty.

The U.K. is one of several countries that allow flexible schedules for authorized vaccines. The U.S. does not and is sticking to the dosing schedule in the Phase III trial.

Public Health England’s findings, published as a preprint in The Lancet, are consistent with Friday’s correspondence in The Lancet on real-world Comirnaty data from Sheba Medical Centre and Tel Aviv University researchers. 

PHE announced one- and two-dose efficacy for the mRNA vaccine against all SARS-CoV-2 infections, including asymptomatic cases, in healthcare workers over 65 years old in its SIREN study. It also reported efficacy against symptomatic disease in individuals over 80. 

In SIREN, the infection rate went down by over 70% after one shot of Comirnaty (BNT162b2) from Pfizer Inc. (NYSE:PFE) and BioNTech SE (NASDAQ:BNTX). Protection increased to 85% after two shots. Eight percent (1,605/19,384) of vaccinated individuals had received a booster by the Feb. 5 cutoff date, with second shots given 19-28 days after the first. The U.K. permits a 22-84 day window after the first shot, and advises a maximum interval of 12 weeks.

The protection in U.K. analysis straddles the 75% efficacy observed in Sheba’s healthcare workers on days 15-28. In that study, the second dose was given on day 21 or 22, so the 15-28-day window corresponded to the end of the single-dose period and the first week after the second dose.

The Israeli study looked even earlier, assessing efficacy during the first two weeks after the first dose, and found a 30% protection rate as the immune response began to build.

Both studies support the idea that protection builds quickly after the first dose of Comirnaty.

SIREN is testing vaccinated and unvaccinated participants for infection every two weeks. The Israel study did not specify its surveillance protocol.

PHE concurrently announced that routine testing revealed one shot was 57% effective against symptomatic disease in individuals over 80 years old, starting four weeks after immunization. Protection went up to 88% seven days after the booster shot.

The findings are in line with Comirnaty’s Phase III data and with Sheba’s real-world study.

In pivotal testing, Comirnaty’s efficacy across all age groups was 52.4% between doses, 90.5% the first week after the booster and 94.8% starting a week after the second shot.

The Sheba analysis of 7,214 vaccinated and 1,895 unvaccinated healthcare workers found that vaccine reduced symptomatic disease by 85% on days 15-28. During the first 14 days after the first shot, efficacy was 47%.

The data from Israel were adjusted to account for the probability of contact with an infected individual given the rates of infection in the community.

The PHE analysis also indicated risk of dying in elderly individuals goes down by at least 56% starting 14 days after the initial vaccination; and those who received at least one dose benefit from a >75% reduction in the risk of hospitalization or death.

In a statement released Monday, PHE wrote, “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.”

The U.K.’s Joint Committee on Vaccination and Immunization (JCVI) advised in a Jan. 6 statement a 12-week maximum interval between the first and second doses Comirnaty. The recommendation also applies to COVID-19 Vaccine AstraZeneca from the University of Oxford and AstraZeneca plc (LSE:AZN; NASDAQ:AZN).

Unlike the U.K., FDA hasn’t budged on dosing schedules, despite calls from prominent figures including former FDA Commissioner Scott Gottlieb and former Operation Warp Speed Chief Scientific Adviser Moncef Slaoui.

In a statement released on Jan. 4, FDA said it wants to “remind the public about the importance of receiving COVID-19 vaccines according to how they’ve been authorized” to achieve the level of protection in the clinical trials that supported their emergency use authorization.

The debate’s issues include the amount of single- vs. two-dose efficacy data, the different ways the data were generated and how the information shapes public trust; the increased risk of viral escape mutants when efficacy is lower; and the public health question of whether it’s better for more people to have partial protection or fewer people to have maximal protection.

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