Reduced levels of convalescent neutralizing antibodies against SARS-CoV-2 B.1+L249S+E484K lineage

Abstract

The E484K mutation at the SARS-CoV-2 Spike protein emerged independently in different variants around the world and has been widely associated with immune escape from neutralizing antibodies generated during previous infection or vaccination. In this work, the B.1 + L249S+E484K lineage was isolated along with A.1, B.1.420, and B.1.111 SARS-CoV-2 lineages without the E484K mutation and the neutralizing titer of convalescent sera was compared using microneutralization assays. While no significant differences in the neutralizing antibody titers were found between A.1 and B.lineages without the E484K mutation, the neutralizing titers against B.1 + L249S+E484K were 1.5, 1.9, 2.1, and 1.3-fold lower than against A.1, B.1.420, B.1.111-I, and B.1.111-II, respectively. However, molecular epidemiological data indicate that there is no increase in the transmissibility rate associated with this new lineage. This study supports the capability of new variants with the E484K mutation to be resistant to neutralization by humoral immunity, and therefore the need to intensify surveillance programs to determine if these lineages represent a risk for public health.

Keywords: COVID-19; E484k mutation; Neutralizing antibodies; SARS-CoV-2 lineages; Spike protein; Variant of Interest.

Fig. 1

Phylogeny of SARS-CoV-2 lineages selected for the MN assays. A.) Representative image of Vero E6 cells infected with SARS-CoV-2. B.) Maximum likelihood phylogeny of SARS-CoV-2 representative lineages by July 2021. The tree was reconstructed by maximum likelihood with the estimated GTR+F+I+G4 nucleotide substitution model for the dataset of 400 genomes. The scale represents nucleotide substitutions per site. The interactive phylogeny and map are available at https://microreact.org/project/fNyvqQHycKrwPjKFMDo6xD/48df9688.

Fig. 2

Neutralizing titers of convalescent sera against SARS-CoV-2 A.1, B.1.420, B.1.111, and B.1 + L249S+E484K lineages. A. Correlation of neutralizing titers against B.1 + L249S+E484K relative to SARS-CoV-2 lineages. B. Neutralizing titers of convalescent sera against SARS-CoV-2 A.1, B.1.420, B.1.111, and B.1 + L249S+E484K lineages. C. B1.111-I sublineage neutralization among convalescent COVID-19 patients and its correlation with SARS-CoV2 IgG anti-Nucleocapsid antibody titers.

Fig. 3

Spatiotemporal distribution of the most representative SARS-CoV-2 lineages in Colombia between January 20,210 and July 2021. A.) SARS-CoV-2 lineage distribution in the five Colombian regions and Bogotá D.C March 2020 - January 20,210 (left), and March-July 2021 (right). Ring colors represent the region. Interactive map available at https://microreact.org/project/sZ7jeqhSJ3bihFGBE1TvVG/0e4c2d4d. Country level SARS-CoV-2 percentages up to January 2021 (left), and up to July 2021 (right).