Emergence and Expansion of the SARS-CoV-2 Variant B.1.526 Identified in New York

Abstract

Recent months have seen surges of SARS-CoV-2 infection across the globe along with considerable viral evolution. Extensive mutations in the spike protein of variants B.1.1.7, B1.351, and P.1 have raised concerns that the efficacy of current vaccines and therapeutic monoclonal antibodies could be threatened. In vitro studies have shown that one mutation, E484K, plays a crucial role in the loss of neutralizing activity of some monoclonal antibodies as well as most convalescent and vaccinee sera against variant B.1.351. In fact, two vaccine trials have recently reported lower protective efficacy in South Africa, where B.1.351 is dominant. To survey for these novel variants in our patient population in New York City, PCR assays were designed to identify viruses with two signature mutations, E484K and N501Y. We observed a steady increase in the detection rate from late December to mid-February, with an alarming rise to 12.3% in the past two weeks. Whole genome sequencing further demonstrated that most of our E484K isolates (n=49/65) fell within a single lineage: NextStrain clade 20C or Pangolin lineage B.1.526. Patients with this novel variant came from diverse neighborhoods in the metropolitan area, and they were on average older and more frequently hospitalized. Phylogenetic analyses of sequences in the database further reveal that this B.1.526 variant is scattered in the Northeast of US, and its unique set of spike mutations may also pose an antigenic challenge for current interventions.

Mutational escape from the polyclonal antibody response to SARS-CoV-2 infection is largely shaped by a single class of antibodies

“…All these emerging viral lineages except B.1.1.7 14,16,[39][40][41] have a mutation that escapes some antibodies from at least one class. The class 2 antibody escape mutation E484K is present in the B.1.351, P.1, P.2 and B.1.526 lineages ( Figure 6C ) 1,2,[4][5][6] . Two of these lineages, B.1.351 and P.1, also have a class 1 antibody escape mutation, K417N or K417T, respectively ( Figure 6C ).…”

“…Control of the SARS-CoV-2 pandemic will depend on widespread population immunity acquired through infection or vaccination. But a little over a year into the pandemic, a proliferating number of new viral lineages are rising in frequency [1][2][3][4][5][6] . These emerging lineages have mutations at <1% of all residues in the viral spike, and at no more than 3 of the ~200 residues in the spike receptor-binding domain (RBD)-yet these handfuls of mutations often substantially erode and in some cases even ablate the polyclonal neutralizing antibody response elicited by infection [7][8][9][10][11][12][13][14][15][16] .…”

“…Instead, the plasma-escape maps usually most resemble a single antibody class ("class 2" in the Barnes et al classification 25 ) that targets the face of the receptor-binding ridge that is accessible in both "up" and "down" RBD conformations. Unfortunately, a mutation that escapes this antibody class (E484K) is present in many emerging viral lineages, including B.1.351, P.1, P.2, and B.1.526 1,2,[4][5][6] . We suggest that domination of the RBD-targeting polyclonal response by a single antibody class is a major factor in enabling a small number of viral mutations to sometimes substantially erode neutralizing antibody immunity.…”

Evolving SARS-CoV-2 variants and mutational cascades

“…These include the UK strain (B.1.1.7/501Y.V1, August 2020), the South Africa strain (B.1.351/501Y.V2, October 2020) and the P.1 lineage identified in Brazil (P.1/501Y.V3, January 2021)(1, 2). Further variants of concern have been reported from Uganda (3), the Philippines (4) and in Northeast US (5).…”

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

“…In the Midwest of the USA, variants with diverse mutations at amino acid position N677 increased in frequency, which, due to N677's proximity to the polybasic S1/S2 cleavage site, potentially affect functional features including viral entry, transmission, and/or spread [346,347]. Most recently, New York variants were detected carrying mostly either the S477N or E484K mutation (Table 2, Figure 6) [348,349]. Since E484K is known to impair nAb efficacy as described for the South African and the Brazilian/Japanese variants, these variants pose an enhanced bias to regional vaccine roll-out.…”