Search bioRxivSearch

Biology subjects

Fafi-Kremer, S.

Publications and source records attributed to Fafi-Kremer, S..

3 recordsLinked to original sources

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

The SARS-CoV-2 B.1.617 lineage emerged in October 2020 in India1-6. It has since then become dominant in some indian regions and further spread to many countries. The lineage includes three main subtypes (B1.617.1, B.1617.2 and B.1.617.3), which harbour diverse Spike mutations in the N-terminal domain (NTD) and the receptor binding domain (RBD) which may increase their immune evasion potential. B.1.617.2 is believed to spread faster than the other versions. Here, we isolated infectious B.1.617.2 from a traveller returning from India. We examined its sensitivity to monoclonal antibodies (mAbs) and to antibodies present in sera from COVID-19 convalescent individuals or vaccine recipients, in comparison to other viral lineages. B.1.617.2 was resistant to neutralization by some anti-NTD and anti-RBD mAbs, including Bamlanivimab, which were impaired in binding to the B.1.617.2 Spike. Sera from convalescent patients collected up to 12 months post symptoms and from Pfizer Comirnaty vaccine recipients were 3 to 6 fold less potent against B.1.617.2, relative to B.1.1.7. Sera from individuals having received one dose of AstraZeneca Vaxzevria barely inhibited B.1.617.2. Thus, B.1.617.2 spread is associated with an escape to antibodies targeting non-RBD and RBD Spike epitopes.

microbiology

Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies

SARS-CoV-2 B.1.1.7 and B.1.351 variants emerged respectively in United Kingdom and South Africa and spread in many countries. Here, we isolated infectious B.1.1.7 and B.1.351 strains and examined their sensitivity to anti-SARS-CoV-2 antibodies present in sera and nasal swabs, in comparison with a D614G reference virus. We established a novel rapid neutralization assay, based on reporter cells that become GFP+ after overnight infection. B.1.1.7 was neutralized by 79/83 sera from convalescent patients collected up to 9 months post symptoms, almost similar to D614G. There was a mean 6-fold reduction in titers and even loss of activity against B.1.351 in 40% of convalescent sera after 9 months. Early sera from 19 vaccinated individuals were almost as potent against B.1.1.7 but less efficacious against B.1.351, when compared to D614G. Nasal swabs from vaccine recipients were not neutralizing, except in individuals who were diagnosed COVID-19+ before vaccination. Thus, faster-spreading variants acquired a partial resistance to humoral immunity generated by natural infection or vaccination, mostly visible in individuals with low antibody levels.

immunology

Evaluation of the performance of SARS-CoV-2 serological tools and their positioning in COVID-19 diagnostic strategies.

Rapid and accurate diagnosis is crucial for successful outbreak containment. During the current coronavirus disease 2019 (COVID-19) public health emergency, the gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosis is the detection of viral RNA by reverse transcription (RT)-PCR. Additional diagnostic methods enabling the detection of current or past SARS-CoV-2 infection would be highly beneficial to ensure the timely diagnosis of all infected and recovered patients. Here, we investigated several serological tools, i.e., two immunochromatographic lateral flow assays (LFA-1 (Biosynex COVID-19 BSS) and LFA-2 (COVID-19 Sign IgM/IgG)) and two enzyme-linked immunosorbent assays (ELISAs) detecting IgA (ELISA-1 Euroimmun), IgM (ELISA-2 EDI) and/or IgG (ELISA-1 and ELISA-2) based on well-characterized panels of serum samples from patients and healthcare workers with PCR-confirmed COVID-19 and from SARS-CoV-2-negative patients. A total of 272 serum samples were used, including 62 serum samples from hospitalized patients (panel 1 and panel 3), 143 serum samples from healthcare workers (panel 2) diagnosed with COVID-19 and 67 serum samples from negative controls. Diagnostic performances of each assay were assessed according to days after symptom onset (dso) and the antigenic format used by manufacturers. We found overall sensitivities ranging from 69% to 93% on panels 1 and 2 and specificities ranging from 83% to 98%. The clinical sensitivity varied greatly according to the panel tested and the dso. The assays we tested showed poor mutual agreement. A thorough selection of serological assays for the detection of ongoing or past infections is advisable.

microbiology