Watching the new Epsilon variant of SARS-CoV-2
Following the reports of increasing displacement of currently circulating SARS-CoV-2 variants by the delta variant (B.1.617.2 lineage), recent reports draw attention to the next variant in line, named Epsilon or B.1.427/B.1.429 variant, reported the European Society Of Clinical Microbiology And Infectious Diseases’ (ESCMID’) Outbreak News.
In the course of this COVID-19 pandemic, two elements are of concern regarding the spread of SARS-CoV-2: the fixation of the spike D614G substitution and the emergence of several viral lineages, accumulating S mutations as well as in other genes. These can result in reduction in the neutralizing potency of several monoclonal antibodies and vaccine-elicited antibodies towards the variants carrying these mutations.
Similar to prior variants of concern, there is evidence for increased transmissibility and some antibody escape This Epsilon variant was reported for the first time at the beginning of 2021 in California; the increased incidence of this lineage, and its progressive geographical spread from California to other US states and other countries is suggestive of enhanced transmissibility, i.e. 18.6% to 24% more than the wild-type circulating strains, and with two- fold increased shedding in vivo, according to a recent article in Cell by Deng X et al.
In a recent article in Science, MacCallum et al. assessed the impact of mutations in the B.1.427/B.1.429 S glycoprotein, comparing the neutralization potency of mRNA vaccine-elicited antibodies against G614 S and B.1.427/B.1.429 S pseudoviruses. They found that the three mutations present in the B1.427/B.1.429 S glycoprotein decreased the neutralizing activity of vaccine-elicited and infection-elicited antibodies, suggesting that the lineage substitutions are associated with immune evasion. Indeed, plasma from individual s vaccinated with an mRNA vaccine or convalescent individuals exhibited neutralizing titres, which were reduced two-three-five fold against the B.1.427/B.1.429 variant compared to wildtype pseudoviruses.
However, these data also underscore the higher quality of antibody response induced by vaccination compared to infection and their enhanced resilience to mutations found in this variant, which was defined as a Variant of Concern (VOC) in the USA. EITaF comment: The Epsilon (B.1.427/B.1.429) lineage is spreading worldwide. According to GISAID, 45 countries, from US to South Korea, from India to Japan have reported Epsilon variant cases. In Europe, cases have been found in Denmark (37), Germany (10), Ireland and France (7), The Netherlands and Spain (5), Switzerland (4) Norway (3) Sweden, Italy and Finland (2) and Belgium (1).
However, its relative incidence appears to be decreasing in the USA, where it was recently downgraded to a Variant of Interest (VOI), and ECDC is monitoring it while the number of isolations in Europe remains low. Understanding the newfound mechanism of immune evasion of the emerging variants, such as the signal peptide modification described in the article, is as important as sequence surveillance itself to successfully counter the ongoing pandemic.
While antibody escape now has been document for several VOC, vaccination remains a cornerstone of the public health response to the pandemic. While not yet available for Epsilon, studies done so far have found limited effect on T cell responses of variant emergence and protection from severe disease. The continued circulation of SARS-CoV-2 and the global disparity in vaccine access, however, are a concern as they provide ample opportunity for emergence of further variants. With reduced impact of the pandemic in countries with earliest access, it is imperative to continue investing in pandemic response and control globally.
