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Detection of SARS-CoV-2 Neutralizing Antibodies using High-Throughput Fluorescent Imaging of Pseudovirus Infection
Published on: June 5, 2021
Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma
Sandile Cele1,2, Inbal Gazy2,3,4, Laurelle Jackson1
1Africa Health Research Institute, Durban, South Africa.
Abstract:
SARS-CoV-2 variants of concern (VOC) have arisen independently at multiple locations1,2 and may reduce the efficacy of current vaccines that target the spike glycoprotein of SARS-CoV-23. Here, using a live-virus neutralization assay, we compared the neutralization of a non-VOC variant with the 501Y.V2 VOC (also known as B.1.351) using plasma collected from adults who were hospitalized with COVID-19 during the two waves of infection in South Africa, the second wave of which was dominated by infections with the 501Y.V2 variant. Sequencing demonstrated that infections of plasma donors from the first wave were with viruses that did not contain the mutations associated with 501Y.V2, except for one infection that contained the E484K substitution in the receptor-binding domain. The 501Y.V2 virus variant was effectively neutralized by plasma from individuals who were infected during the second wave. The first-wave virus variant was effectively neutralized by plasma from first-wave infections. However, the 501Y.V2 variant was poorly cross-neutralized by plasma from individuals with first-wave infections; the efficacy was reduced by 15.1-fold relative to neutralization of 501Y.V2 by plasma from individuals infected in the second wave. By contrast, cross-neutralization of first-wave virus variants using plasma from individuals with second-wave infections was more effective, showing only a 2.3-fold decrease relative to neutralization of first-wave virus variants by plasma from individuals infected in the first wave. Although we tested only one plasma sample from an individual infected with a SARS-CoV-2 variant with only the E484K substitution, this plasma sample potently neutralized both variants. The observed effective neutralization of first-wave virus by plasma from individuals infected with 501Y.V2 provides preliminary evidence that vaccines based on VOC sequences could retain activity against other circulating SARS-CoV-2 lineages.
Insights
Neutralizing antibodies from South African COVID-19 patients show reduced efficacy against the 501Y.V2 variant. However, vaccines based on variants of concern may retain activity against other SARS-CoV-2 lineages.
Area of Science:
- Virology
- Immunology
- Epidemiology
Background:
- SARS-CoV-2 variants of concern (VOC) can emerge independently and potentially reduce vaccine efficacy.
- The 501Y.V2 (B.1.351) VOC emerged during the second wave of COVID-19 infections in South Africa.
- Understanding variant neutralization is crucial for vaccine development and public health strategies.
Purpose of the Study:
- To compare the neutralization of a non-VOC SARS-CoV-2 variant with the 501Y.V2 VOC.
- To assess the efficacy of plasma from individuals infected during different waves in South Africa against these variants.
- To provide evidence for the potential effectiveness of vaccines based on VOC sequences.
Main Methods:
- Live-virus neutralization assays were performed using plasma from COVID-19 patients hospitalized during two infection waves in South Africa.
- Viral sequencing was used to characterize the SARS-CoV-2 strains involved in first-wave infections.
- Neutralization efficacy was measured by comparing antibody responses against the non-VOC and 501Y.V2 variants.
Main Results:
- Plasma from the second wave effectively neutralized the 501Y.V2 variant.
- Plasma from the first wave poorly cross-neutralized the 501Y.V2 variant (15.1-fold reduction).
- Cross-neutralization of first-wave variants by second-wave plasma was more effective (2.3-fold reduction).
Conclusions:
- The 501Y.V2 variant exhibits reduced neutralization by plasma from earlier infections.
- Vaccines designed using VOC sequences may offer protection against other circulating SARS-CoV-2 lineages.
- This suggests potential cross-protection capabilities of vaccines targeting variant spike glycoproteins.

