Reduced sensitivity of commercial Spike-specific antibody assays after primary infection with the SARS-CoV-2 Omicron variant

Abstract

ObjectivesThe SARS-CoV-2 Omicron variant is characterized by substantial changes in the antigenic structure of the Spike (S) protein. Therefore, antibodies induced by primary Omicron infection lack neutralizing activity against earlier variants. In this study, we analyzed whether these antigenic changes impact the sensitivity of commercial anti-SARS-CoV-2 antibody assays. MethodsSera from 37 unvaccinated, convalescent individuals after primary Omicron infection were tested with a panel of 20 commercial anti-SARS-CoV-2 immunoassays. As controls, we used samples from 43 individuals after primary infection with the SARS-CoV-2 ancestral wildtype strain. In addition, variant-specific live-virus neutralization assays were used as a reference for the presence of SARS-CoV-2-specific antibodies in the samples. Results Notably, in Omicron convalescents, there was a statistically significant reduction in the sensitivity of all antibody assays containing S or its receptor-binding-domain (RBD) as antigens. Furthermore, antibody levels quantified by these assays displayed a weaker correlation with Omicron-specific neutralizing antibody titers than with those against the wildtype. In contrast, the sensitivity of nucleocapsid-protein-specific immunoassays was similar in wildtype and Omicron-infected subjects. ConclusionsIn summary, the antigenic changes in the Omicron S lead to reduced detection rates in commercial S- and RBD-specific antibody assays, impairing their diagnostic performance.

Seroprevalence of Antibodies to SARS-CoV-2 in Rural Households in Eastern Uganda, 2020-2022

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Reconstructing the SARS-CoV-2 epidemic in eastern Uganda through longitudinal serosurveillance in a malaria cohort

“…Our results suggest a higher attack rate during the first Omicron wave of SARS-CoV-2 than the Delta wave (85% vs 47%), and the high estimated re-infection rate during Omicron (51%) is consistent with the evidence of increased infectivity and immune evasion associated with this variant 24,25 . Due to the antigenic changes in the spike protein of the Omicron variant, the sensitivity of existing assays measuring spike antibody responses may be reduced against this variant 26 . Gold standard serologic assays are needed to accurately determine re-infections, possibly with variant-specific assays.…”

Neutralization of SARS‐CoV‐2 Omicron XBB.1.5 and JN.1 variants after COVID‐19 booster‐vaccination and infection

“…SARS-CoV-2 strains were amplified on VeroE6 (ECACC #85020206) or VeroE6-TMPRSS2 cells (courtesy of Anna Ohradanova-Repic), as described previously. [11][12][13][14] Sequences determined by next-generation sequencing were uploaded to the GISAID database (Supporting Information S1: Table S1). 13 Live-virus NTs were conducted as described earlier.…”

“…13 Live-virus NTs were conducted as described earlier. [11][12][13][14] In brief, 50-100 TCID 50 SARS-CoV-2 were incubated with serial two-fold dilutions from 1:10 up to 1:20,480 of heat-inactivated serum (in duplicates) for 1 h at 37°C. The sample-virus mixture was added to VeroE6 cells and incubated for 3-5 days at 37°C.…”