On December 30, 2020, the United Kingdom announced a deviation from the recommended protocol for the Pfizer-BioNTech covid-19 vaccine, extending the interval between doses from 3 to 12 weeks . Similar decisions were made for the Oxford-AstraZeneca vaccine, for which a longer interval between doses has been shown to improve efficacy in some age groups.
The stated intention was to maximize profit with limited supplies and minimize hospital admissions and deaths. For the Pfizer-BioNTech vaccine, the decision to delay the second dose was based on extrapolations from Phase III trial data showing 89% efficacy between 15 and 21 days after the first dose. At the time, Pfizer did not support the decision, stating that high efficacy could not be guaranteed.
Efficacy in older people appears excellent after two doses of the Pfizer-BioNTech vaccine. A longer interval between doses may improve the long-term immune response, as seen with the AstraZeneca vaccine. However, as many people in priority subgroups have not yet received a second dose, any substantial drop in protection over the 12-week interval will create problems as the UK begins to reopen.
This is of particular concern for older adults. The Phase II trial of the Pfizer-BioNTech vaccine reported a reduced antibody response among participants aged 65 to 85 compared to those under 55. Recent data from Public Health England showed that efficacy against symptomatic disease was 57% among adults over 80 after a single dose, increasing to 85% after the second dose.
This is consistent with antibody surveillance data from the React-2 study, 10 which showed IgG positivity 21 days after a dose of the Pfizer-BioNTech vaccine in 80% of adults under 60 years of age, but only in 49 % and 34% of those over 70 years of age. and 80, respectively. IgG positivity increased to 93% and 88%, respectively, after a second dose, suggesting that the second dose is critical in these vulnerable age groups.
Data from Public Health Scotland showed that effectiveness against hospital admission decreased from 35 days after the first dose, although as the results were not reported by age, it is not clear whether these are age cohort effects or related to decreased immunity, or both.
Real-world data (not yet peer-reviewed) suggests promising efficacy of the Pfizer-BioNTech vaccine among older adults. In Israel, where most people over 60 have already received two doses of the vaccine, surveillance data show a marked divergence in hospital admission and death rates between vaccinated and unvaccinated age groups.
Threats of variants
The new SARS-Co-V-2 variants complicate this picture. A study published as preprint14 found a neutralizing antibody response against the B.1 variant (first discovered in the United Kingdom) in eight of 15 participants over 80 years, 21 days after a dose of the Pfizer-BioNTech vaccine, in compared to 100% in those under 80 years of age.
In a pre-print subanalysis of 256 participants who tested positive for Covid-19 during the Phase II/III AstraZeneca vaccine trial, the vaccine appeared to remain highly effective against the B.1 variant but the efficacy of the doses singles and doubles was once again not reported by age. This is a substantial gap in our knowledge of both vaccines.
Taken together, the current evidence suggests legitimate concerns about the effectiveness of these vaccines in older adults after a single dose, including the durability of the immune response.
There is even less evidence available on the effectiveness of these vaccines against the B.1.351 variant (first identified in South Africa) or newer variants identified in the United Kingdom that also express the E484K mutation associated with immune escape.
Early data from Novavax, 16 Johnson & Johnson, 17 AstraZeneca, 18 Pfizer-BioNTech, and Moderna19 suggest that the vaccines may be less effective against the B.1.351 variant, at least for mild to moderate disease. These findings highlight the threat posed by virus adaptation and the emergence of escape mutations. A single-dose strategy may exacerbate this threat, according to some modeling studies.
Governments currently rolling out vaccines should mitigate the uncertainty associated with deviations from recommended vaccine protocols by delivering vaccines within a robust testing framework. This would help address missing data, provide early warning of potential harms, and allow rapid modification of vaccination programs globally if necessary.
At the same time, studies should be conducted to identify correlates of immunity among vaccinated people over time so that policies can be quickly adapted to ensure adequate protection. Greater data transparency is also required for older adults, as all vaccines are currently rolled out primarily to these age groups.
As potential vaccine-resistant variants continue to circulate in the UK, the need for a clear exit strategy from the pandemic has never been greater. Effective suppression of transmission remains essential to prevent the emergence and spread of new variants capable of escaping vaccine-acquired immunity.
Measures such as test, trace and supported isolation, along with mass vaccination and strict border controls, are the only logical way to ensure that this third lockdown is truly the last in the UK.
