Profound immune escape by SARS-CoV-2 XBB.1 even after 4 vaccine doses

By Bhavana KunkalikarReviewed by Danielle Ellis, B.Sc.Jan 9 2023

In a recent correspondence published in The Lancet Infectious Diseases journal, researchers in Germany assessed the neutralization sensitivity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) XBB.1 lineage.

Co-infection with different SARS-CoV-2 lineages can lead to the recombination of the distinct viral genomes and the creation of new and recombinant SARS-CoV-2 lineages. First detected in India in January 2022, the recombinant XBB lineage is spreading rapidly throughout Europe and Asia. The XBB lineage was formed due to the recombination of two SARS-CoV-2 Omicron variant sublineages, namely BM.1.1.1 and BJ.1. The breakpoint of this novel lineage is located within the spike protein gene, which facilitates viral entry into the host cell and comprises the target of neutralizing antibodies. So far, five primary XBB sublineages have evolved, with XBB.1 accounting for most coronavirus disease 2019 (COVID-19) cases.

Correspondence: Neutralisation sensitivity of the SARS-CoV-2 XBB.1 lineage. Image Credit: Corona Borealis Studio / Shutterstock

About the study

In the present study, researchers reported the efficiency with which the SARS-CoV-2 XBB.1 lineage can enter the host cell and evade antibody-mediated neutralization.

The team employed pseudovirus particles (_pp) carrying the SARS-CoV-2 spike protein that served as a suitable model for studying SARS-CoV-2 entry in the host cell and its subsequent neutralization. Particles that were pseudotyped with the ancestral SARS-CoV-2 B.1 (B.1_pp) or the Omicron BA.5 (BA.5_pp) lineage were utilized for comparison. Furthermore, the team analyzed the neutralization sensitivity of XBB.1_pp by monoclonal antibodies (mAbs) and the mAb cocktails currently used clinically or in development for COVID-19 therapy or prophylaxis.    

The team also analyzed the sensitivity of XBB.1_pp to neutralization by COVID-19 vaccination or vaccination along with breakthrough infection. Furthermore, plasma samples from triple-vaccinated persons having breakthrough COVID-19 infections during BA.5 prevalence in Germany were assessed.

Results

The study results showed that in comparison to B.1_pp, the BA.5_pp showed 2.2-fold higher efficiency in entering Vero cells and 5.3-fold higher efficiency in entering 293T cells. On the other hand, the efficiency of BA.5_pp entering Calu-3 cells was 1.9-fold lesser than that of B.1_pp. Additionally, particles that carried the XBB.1 spike protein (XBB.1_pp) displayed remarkably decreased efficiency in cell entry compared to BA.5_pp for all the cell lines assessed. However, the entry efficiency of B.1_pp and XBB.1_pp was comparable to that of Vero and 293T cells.

The team also noted that all the analyzed mAbs and mAb cocktails effectively neutralized B.1_pp while XBB.1_pp was neutralized by only sotrovimab and S2H97. Also, the efficiency of XBB.1_pp neutralization decreased by over 10 times compared to B.1_pp neutralization. Additionally, plasma obtained from triple-vaccinated persons had almost no XBB.1_pp neutralization activity. On the other hand, B.1_pp neutralizing activity was high while that against BA.5_pp was intermediate. The plasma samples of triple-vaccinated persons with breakthrough infection showed high B.1_pp neutralizing activity, moderate BA.5_pp neutralizing activity, and low XBB.1_pp neutralizing activity.

Overall, the study findings showed that the SARS-CoV-2 XBB.1 lineage has an exceptionally robust antibody evasion activity. The researchers believe that the finding that XBB.1_pp was not neutralized by mAbs highlights the need for novel mAbs for COVID-19 treatment along with additional therapeutic options for locations with high cases of XBB lineage infections.