COVID-19 vaccine efficacy data: solid enough to delay second dose?

Sharon Amit and colleagues suggest that after a first dose of BNT162b2 vaccine, there was an adjusted rate reduction of COVID-19 disease of 85% (71–92) for days 15–28 in vaccinated compared with unvaccinated health-care workers (HCWs). We think this Correspondence has fundamental flaws and address them here.

First, HCWs have been shown to have higher risks for SARS-CoV-2 viral infection, which result in asymptomatic, pre-symptomatic (at time of study initiation), or symptomatic infection.2, 3

Second, individuals documented to have had a SARS-CoV-2 viral infection have a substantially greater response to the first dose of vaccine (up to over a thousand times the neutralising antibodies before the first vaccine dose), which is much greater than the level of response seen through natural infection and also after the second dose of vaccine in individuals who are naive in terms of previous exposure to SARS-CoV-2 virus.4, 5

Third, the reported 47% reduction in infection rates on days 1–14 does not mirror findings reported in any of the phase 3 randomised clinical trials including populations that were mostly virus-naive individuals6, 7, 8 or in preliminary analyses9, 10 of much larger population-based cohorts than that described by Amit and colleagues.

The immunologically straightforward explanation of these results is that the first dose of BNT162b2 was given to a population of HCWs, a substantial proportion of whom had been exposed to the SARS-CoV-2 infection and therefore the first dose of vaccine was, in essence, equivalent to a booster dose generating a secondary immune response. How else could the infection rate reduction between days 1–14 be explained?

Of note, the difference on days 1–14 (47% vaccine efficacy) and days 15–28 (85%) is 38%, which lies within other estimates of vaccine efficacy for the much larger population cohorts from Israel (33–59% rate of reduction).

Additionally, the reporting days for infections in this study (days 15–28) are not only unusual, given that the second dose is scheduled for day 22, but also hide the fact that if only a single dose was given, the neutralising antibodies would be falling by days 22–28 (with decreasing immunity) rather than rising quickly as they do with a second dose of mRNA vaccine.

On this basis, we feel the authors should withdraw their Correspondence until they can provide a more substantive report with all the appropriate serology of these HCWs before the first vaccine dose.

The UK Government and Public Heath England, along with the general media, have seized these results to support and justify the UK policy of delaying the second dose of BNT162b2 to 12 weeks, but our concerns need to be addressed to ensure scientific rigour. As we have noted previously, we have reason to believe delaying the second dose of BNT162b2 carries considerable personal and population risks.

JFRR holds shares and was a Director and Chief Scientific Officer, 2003–13, at Oncimmune, which was spun out from the University of Nottingham, UK, as a company for early diagnosis of cancer using detection of autoantibodies to cancer antigens. In 2020, Oncimmune used the technology platform for measuring antibodies to SARS-COV-2 antigens; JFRR had not been involved in this development. HFS declares no competing interests.