“The Great Escape” by SARS-CoV-2 XBB.1


In a recent article in Lancet Microberesearchers in the Netherlands and the United Kingdom quantified the antigenic diversity of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sub-variants, BQ.1.1, BM.1.1.1, and XBB.1, all variant (VOC) derivatives. Omicron, which appeared in late 2022. This exercise may prove fruitful in identifying SARS-CoV-2 strains for the next generation of coronavirus disease 2019 (COVID-19) vaccines.

Conformity: antigenic mapping of emerging SARS-CoV-2 Omicron variants BM.1.1, BQ.1.1, and XBB.1.  Image credit: NIAID

Correspondence: Antigenic mapping of emerging SARS-CoV-2 Omicron variants BM.1.1.1, BQ.1.1 and XBB.1. Image credit: NIAID

background

It is extremely alarming that new sub-variants of Omicron are emerging at an exceptional rate, despite vaccination and previous infection-induced immunity in the majority of the world’s population.

about studying

In this study, the researchers used antigenic mapping to simultaneously identify and visualize the antigenic properties of SARS-CoV-2 variants. This multidimensional measurement method is widely used by researchers to be sure antigen positions versus serum samples, both correspond directly to neutralizing antibody titers.

They used a SARS-CoV-2 hamster model for their experiments. First, they infected test animals with an Omicron BA.5 variant, genetically close to Omicron BA.2, but altered by two deletions and three substitutions in the spike (S) amino acid sequence. Next, they evaluated the neutralizing antibody titers of all serum samples and variants, including Omicron BA.5, BM.1.1.1, BQ.1.1 and XBB.1.

Results and conclusion

The updated antigenic map generated shows that all Omicron sub-variants were positioned further from the previous Omicron sub-variants, with one antigenic unit reflecting a twofold decrease in neutralizing titers. Specifically, only BA.5 and BA.2, being homozygous variants, occupied antigenic sites within a single antigenic unit, while the remaining Omicron sub-variants retained antigen positions 2.3 to seven antigenic units distant from each other.

Moreover, study data revealed that Omicron BA.5 antiserum samples significantly neutralized BA.2 and BQ.1.1 but not Omicron BM.1.1.1. Remarkably, none of the serum samples effectively neutralized Omicron XBB.1. In both two-dimensional (2D) and three-dimensional (3D) maps, Omicron XBB.1, BM.1.1.1 and BQ.1.1 were the furthest away from all of the previous variants, with no significant improvement with the larger number of dimensions. The authors observed a correlation between antigen map distances and neutralizing antibody titers with remarkable precision in positioning the antigen sample and the serum sample. They also observed the highest decrease in neutralization titers for BQ.1.1, XBB.1 and BM.1.1.1, followed by Omicron BA.5 and BA.1/BA.2 compared to D614G, the ancestral SARS-CoV-2. -2 strain.

In conclusion, none of the new Omicron subtype variants clustered close to each other on antigenic maps. Therefore, despite the antigenic similarities between BQ.1.1 and BA.5, immunological imprinting may hinder BQ.1.1 neutralization by bivalent BA.5-based vaccines. Furthermore, a vaccine based on any of the sub-Omicron variants may weakly neutralize not yet demonstrated SARS-CoV-2 variants, which may be of equal or more antigenic distance. Therefore, it is imperative to continuously identify new SARS-CoV-2 variants and develop an understanding of their evolutionary trajectory to inform the development of future COVID-19 vaccine candidates.

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