Pfizer and BioNTech on Wednesday reported results from another in-vitro study indicating that their COVID-19 vaccine BNT162b2 is likely capable of neutralizing the rapidly spreading UK strain of SARS-CoV-2, also known as B.1.1.7. The findings, which were published on the preprint server bioRxiv, follow the release of a similar laboratory study earlier this month showing that antibodies from vaccinated people were able to efficiently neutralize variants of SARS-CoV-2 with a key mutation, dubbed N501Y, found in the UK variant, as well as another highly transmissible strain that has emerged in South Africa.
The B.1.1.7 lineage, also referred to as VOC 202012/01, carries a “larger than usual number of genetic changes with 10 mutations located in the spike protein,” the companies said, adding that in contrast with the first study, which focused on N501Y-mutant SARS-CoV-2, the current in-vitro work looked at the full set of UK strain spike mutations.
Biologically ‘equivalent’ neutralisation
For the latest study, pseudoviruses were generated bearing either the Wuhan reference strain or the B.1.1.7 lineage spike protein. Pfizer and BioNTech pointed out that while the pseudovirus system represents a surrogate for the real virus, there has been “excellent concordance” between pseudotype and SARS-CoV-2 neutralisation assays in previous studies.
Researchers found that the sera of 16 participants in a previously reported German phase 1/2 trial of BNT162b2 induced “equivalent” neutralizing titers to both the UK strain and the unmutated Wuhan SARS-CoV-2 spike. These findings, “together with the combined immunity involving humoral and cellular effectors induced by this vaccine, make it unlikely that the B.1.1.7 lineage will escape BNT162b2-mediated protection,” the authors said.
Ready to adapt
Pfizer and BioNTech’s mRNA-based vaccine, which was found to be 95% effective in a phase 3 trial after two doses given 21 days apart, is already authorized in several countries including the UK, US and Europe, where it is branded as Comirnaty. The companies say they are “encouraged” by the new study, but cautioned that more data are needed to monitor the vaccine’s effectiveness at preventing COVID-19 caused by new variants. It is not yet clear what level of reduced efficacy would warrant a vaccine strain change, but they indicated that should such a change be necessary in the future, “the flexibility of BioNTech’s proprietary mRNA vaccine platform is well suited to enable such adjustment.”
A separate study conducted by researchers in South Africa has raised concern that the South African variant of SARS-CoV-2 may be harder to protect against. The findings, which have not yet been peer-reviewed, showed that half of the blood samples from a handful of patients who already had COVID-19 do not have the antibodies needed to protect against the South African variant, while antibody levels in the other half were reduced and the risk of re-infection could not be determined. In yet another study, US scientists tested mutations found in the UK and South African variants, as well as a strain that has surfaced in Brazil, in blood samples from 20 volunteers who had received either the Pfizer/BioNTech vaccine or Moderna’s similar candidate, mRNA-1273. Their work, which was also presented in pre-print, showed the donors’ blood samples were not quite as effective at neutralizing the variants.
Doubts on delayed dosing
Meanwhile, researchers in Israel say the first real-world analysis of Pfizer and BioNTech’s vaccine is casting doubt on the UK’s policy to delay the second dose in order to stretch out supply, a move being considered in other countries as well, including the US. The Israeli scientists compared 200,000 people over the age of 60 who were vaccinated to a matched group of 200,000 unvaccinated individuals, and found no difference between the two groups until 14 days after the first immunisation was given, when the vaccinated group saw a 33% drop in infection rates. That contrasts with claims by UK scientists that the vaccine was 89% effective after only one dose, and is also lower than the 52% effectiveness reported by Pfizer and BioNTech for a single dose. The Israeli scientists also believe that the effectiveness of one dose of the vaccine in a real-world setting will rise when data is compiled from younger age groups.
On the flip side, results reported recently from a serological trial of 102 people at Israel’s Sheba Medical Center showed that a week after the second dose of Pfizer and BioNTech’s vaccine, over 98% presented a much higher level of antibodies than required to be considered immune. Although a week before receiving the second dose, the study found that only 50% of those examined had levels of antibodies considered sufficient for protection.