SARS-CoV-2 B.1.617.2 Delta variant replication, sensitivity to neutralising antibodies and vaccine breakthrough

Abstract

The B.1.617 variant emerged in the Indian state of Maharashtra in late 2020 and has spread throughout India and to at least 40 countries. There have been fears that two key mutations seen in the receptor binding domain L452R and E484Q would have additive effects on evasion of neutralising antibodies. Here we delineate the phylogenetics of B.1.617 and spike mutation frequencies, in the context of others bearing L452R. The defining mutations in B.1.617.1 spike are L452R and E484Q in the RBD that interacts with ACE2 and is the target of neutralising antibodies. All B.1.617 viruses have the P681R mutation in the polybasic cleavage site region in spike. We report that B.1.617.1 spike bearing L452R, E484Q and P681R mediates entry into cells with slightly reduced efficiency compared to Wuhan-1. This spike confers modestly reduced sensitivity to BNT162b2 mRNA vaccine-elicited antibodies that is similar in magnitude to the loss of sensitivity conferred by L452R or E484Q alone. Furthermore we show that the P681R mutation significantly augments syncytium formation upon the B.1.617.1 spike protein, potentially contributing to increased pathogenesis observed in hamsters and infection growth rates observed in humans.

Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals

“…India is facing a large surge in COVID-19 cases since early 2021. Many cases are caused by a new lineage, termed B.1.617 [1][2][3][4][5][6] . The epidemiology data are scarce, but B.1.617 has become the predominant strain in the state of Maharashtra and probably in other Indian regions 4 .…”

“…This lineage is under evolution and has been subdivided into three main sublineages, B.1.617.1, B.1.617.2 and B.1.617.3 29 The B.1.617.2 sublineage has been recently classified as a VOC, since it is believed to be more transmissible than the two other sublineages. Recent pre-prints reported a reduced sensitivity of B.1.617 to certain monoclonal and polyclonal antibodies [1][2][3][4][5][6]30 . Experiments were so far mostly performed with single-cycle pseudotyped viral particles, and very little is known about the sensitivity of replicative B.1.617.2 to the humoral immune response.…”

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The SARS-CoV-2 B.1.617 lineage emerged in October 2020 in India [1][2][3][4][5][6] . It has since then become dominant in some indian regions and further spread to many countries.

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Trajectory of Growth of SARS-CoV-2 Variants in Houston, Texas, January through May 2021 Based on 12,476 Genome Sequences

“…We also identified seven patients with COVID-19 caused by B.1.617.1 or B.1.617.2, variants reported to be causing widespread disease and extensive public health concern in India. [43][44][45][46][47][48] In the aggregate, our genome data show that VOC and VOI now account for the great majority of all new COVID-19 cases in our region.…”

Second wave of COVID-19 in India could be predicted with genomic surveillance of SARS-CoV-2 variants coupled with epidemiological data: A tool for future

“…alpha variant), which had been a dominant strain in Indian population before the arrival of second wave (1). The studies have shown a significant reduction in the neutralization against B.1.617 lineage variants by antibodies received from natural infections and manycurrently used COVID-19 vaccines and multiple monoclonal antibodies (5)(6)(7)(8). Higher transmissibility and immunoescape is being reported for B.1.617.2, which is currently the fastest growing SARS-CoV-2 strain in the Indian population (1,(9)(10).…”