#16,310
Two weeks ago, in UKHSA Technical Briefing On Delta Sub-Lineage AY.4.2, we saw some early reports that it might be slightly more transmissible than the Delta B.1.617.2 parental strain.
Today Denmark's Staten Serum Institut (SSI) published a summary of a pre-print (published yesterday in MedRxiv), which looks at the VE (Vaccine Effectiveness) of the mRNA COVID vaccine - based on lab tests using serum from Pfizer-BioNTech vaccinated individuals - against this AY.4.2 subvariant.
The news isn't quite as good for the (far less common) B.1.617.2+E484K variant, which exhibited a much higher (4.2 fold) reduction in virus neutralization - comparable to what we've seen with the Beta variant - (see excerpt below).While AY.4.2 has a slightly reduced sensitivity to neutralizing vaccine antibodies compared to the original pandemic strain, the good news is that it doesn't appear to have any greater ability to evade the current vaccine than its parental Delta strain.
We further evaluated a B.1.617.2 lineage isolate that contains the E484K amino acid substitution in the receptor binding domain. In contrast to AY.4.2, B.1.617.2 with E484K had significant 4.2-fold reduction in virus neutralisation titers relative to B.1.617.2 and AY.4 (median titer: 46 vs. 128 and 118, respectively; P < 0.050 for both comparisons).
For now, Beta and B.1.617.2 with E484K haven't demonstrated the ability to compete successfully with dominant Delta strain, but they remain variants very much worth monitoring. First the (translated) Summary, followed by a the Abstract from, and link to. the full preprint.
The new Delta subvariant AY.4.2 shows no evidence of diminished vaccine efficacy
Researchers from the Statens Serum Institut have, like the first in the world, succeeded in cultivating Delta AY.4.2 in security laboratories at SSI, so that it has been possible to investigate it further.Last edited November 10, 2021
New variants of SARS-CoV are constantly emerging. Most recently, attention has been focused on the Delta AY.4.2 sub-variant, which is on the rise in the UK, among other places. Here it now accounts for more than 12% of the sequenced samples.
Cultivated at SSI
Denmark is at the forefront when it comes to examining the new sub-variant. As the first in the world, researchers at the Statens Serum Institut (SSI) have succeeded in cultivating Delta AY.4.2 in security laboratories at SSI.
Here, AY.4.2 has been tested by exposing it to antibody serum from 14 people vaccinated with the covid-19 vaccine from Pfizer / Biontech. If one compares the results with results from other SARS-CoV variants, it turns out that AY.4.2 has a slightly reduced sensitivity to neutralizing vaccine antibodies compared to the original Wuhan-like virus contained in the vaccines.
“But Delta AY.4.2 has not reduced sensitivity compared to the other Delta variants. And thus not a reduced vaccine effectiveness. Therefore, it is probably not an altered antibody sensitivity that is behind the increased number of Delta AY.4.2 cases seen in some areas and countries, ”says chief physician Anders Fomsgaard from SSI.
Delta AY.4.2 in Denmark and Europe
The new sub-variant is found in several countries in Europe. However, the European Center for Disease Prevention and Control (ECDC) does not consider it necessary to classify it as a Variant Of Interest (VOI), as there is no general increasing trend in the EEA countries.
In Denmark, the first case of Delta AY.4.2 was detected on 4 August. By September, the incidence had increased to over 2% of the sequenced samples. However, it fell below 1% over a long period. In the most recent week (week 43), however, the incidence of Delta AY.4.2 has risen to 2% again.
"So far, we do not believe there is cause for concern based on the available data. But of course we follow the situation closely ", says Anders Fomsgaard.
Read more
SSi's research findings have already been published in the online journal RivxMed before being peer-reviewed.
Facts about Delta AY.4.2.
Delta AY.4.2 is a new sub-variant among the now over 100 SARS-CoV-2 Delta variants.
Delta AY.4.2 is characterized by mutations A222V and Y145H in the spike protein.
Preliminary epidemiological studies from the United Kingdom suggest that Delta AY.4.2 is slightly more contagious than other Delta variants, but this has not been definitively determined.
There is no evidence that Delta AY.4.2 causes a more severe disease course or increased mortality than other Delta variants.
Neutralisation of SARS-CoV-2 Delta sub-lineage AY.4.2 and B.1.617.2+E484K by BNT162b2 mRNA vaccine-elicited sera
Ria Lassauniere, Charlotta Polacek, Jannik Fonager, Marc Bennedbaek, Lasse Boding, Morten Rasmussen, Anders Fomsgaard
doi: https://doi.org/10.1101/2021.11.08.21266075ABSTRACTA sublineage of the Delta variant, AY.4.2, recently accounted for an increase proportion of Delta cases in United Kingdom (UK), Romania, Poland, and Denmark. Several factors may account for the increased spread of AY.4.2. Here, we evaluated the sensitivity of AY.4.2 to neutralisation by sera from Pfizer/BioNTech (BNT162b2) vaccinees.
AY.4.2 was not more resistant to neutralisation relative to other circulating Delta lineages or sublineages and showed only a modest 2.3-fold reduction in neutralisation relative to the vaccine strain. In contrast, the more rare B.1.617.2+E484K variant showed a 4.2-fold reduction in neutralisation that warrants surveillance of strains with the acquired E484K mutation.
(SNIP)
Discussion and conclusions
In addition to the spike mutations present in the prevalent AY.4 sublineage, AY.4.2 bears the Y145H and A222V amino acid substitutions. Both occur in the N-terminal domain of the spike protein. A222V has been observed in earlier emerging SARS-CoV-2 variants, but is not considered to contribute to increased transmissibility or immune escape in those variants [12]. A functional consequence for Y145H remains to be established.
Using a live virus neutralisation assay, we demonstrate that the Delta sublineage AY.4.2 virus has a modest reduction of 2.3-fold relative to an early pandemic strain, which is highly homologous to the current vaccine strains. AY.4.2 therefore remains sensitive to vaccine-induced virus neutralisation. Moreover, neutralisation titers for AY.4.2 were not significantly different from the parental B.1.617.2 or AY.4 lineage.
It is thus unlikely that neutralisation resistance is a determinant of the increased spread observed for AY.4.2 relative to other Delta lineages in European countries. These findings are in agreement with a similar vaccine effectiveness observed for AY4.2 compared to non-AY4.2 Delta cases, both symptomatic and asymptomatic, for the Astra Zeneca, Pfizer/BioNTech and Moderna vaccines in the UK [2].
On the contrary, we show a significant neutralisation resistance for a Delta variant that acquired the E484K spike mutation. This amino acid substitution in the receptor-binding domain, occur in other VOC that include Beta and Gamma with reduced sensitivity to monoclonal antibodies and vaccine elicited anti-sera [6, 13, 14].
While Delta variants bearing the latter mutation occur mostly sporadically [7], it has occurred in Delta sublineages with sustained clusters recently reported in the UK [2]. The presented data provide further support for continuous monitoring of E484K within emerging Delta sublineages such as the Delta strain examined here.
