The “great escape” by SARS-CoV-2 XBB.1

In a recent article published in the Lancet Microberesearchers in the Netherlands and the UK have quantified the antigenic diversity of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subvariants, BQ.1.1, BM.1.1.1 and XBB.1 , all derived from the Omicron variant of concern (COV), which emerged in late 2022. This exercise could prove fruitful in identifying SARS-CoV-2 strains for vaccines against next-generation coronavirus disease 2019 (COVID-19 ).

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 of great concern that new subvariants of Omicron are emerging at an extraordinary rate, despite vaccination and immunity induced by previous infection in the majority of the world’s population.

About the study

In the current study, researchers used antigenic mapping to simultaneously quantify and visualize the antigenic characteristics of SARS-CoV-2 variants. Researchers use this multidimensional scaling method widely to determine antigen positions with respect to the antiserum samples, both corresponding directly to neutralizing antibody securities.

They used a SARS-CoV-2 hamster model for their experiments. First, they infected test animals with the Omicron BA.5 subvariant, genetically close to Omicron BA.2, but varying by two deletions and three substitutions in the spike amino acid sequence (S). Next, they assessed neutralizing antibody titers for 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 thus generated showed that all Omicron subvariants were positioned farther from the pre-Omicron subvariants, one antigenic unit reflecting a two-fold reduction in neutralization titers. Specifically, only BA.5 and BA.2, being homologous variants, held antigenic positions within one antigenic unit, while the remaining Omicron subvariants held antigenic positions 2.3 to seven antigenic units further apart. one from the other.

In addition, study data revealed that Omicron BA.5 antiserum samples substantially neutralized BA.2 and BQ.1.1, but not Omicron BM.1.1.1. Surprisingly, none of the serum samples effectively neutralized Omicron XBB.1. In two-dimensional (2D) and three-dimensional (3D) boards, Omicron XBB.1, BM.1.1.1, and BQ.1.1 were the farthest from all previous variants, with no marked improvement with the higher number of dimensions. . Researchers observed a correlation between antigen map distances and antibody neutralization titers with remarkable accuracy in the positioning of antigen and serum samples. Additionally, they noted the greatest reduction in neutralizing 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, SARS -Ancestral CoV. -2 stump.

In conclusion, none of the new Omicron subvariants clustered next to each other on the antigenic maps. Thus, despite the antigenic similarities between BQ.1.1 and BA.5, the immunological fingerprint could hinder the neutralization of BQ.1.1 by bivalent vaccines based on BA.5. Additionally, a vaccine based on one of Omicron’s subvariants could weakly neutralize yet-to-emerge SARS-CoV-2 variants, which may be equally or more antigenically distant. Therefore, it is crucial to continuously map new SARS-CoV-2 variants and develop an understanding of their evolutionary trajectory to inform the development of COVID-19 vaccine candidates for the future.

Antigenic distance mapping of XBB.1 (among others):
“We observed that human post-vaccination neutralization titers reflected the antigenic map, as the greatest reduction in neutralizing titers compared to the D614G variant” https://t.co/epa5txNqqw @LancetMicrobe @bart_haagmans pic.twitter.com/oEIeUKt8HR

— Eric Topol (@EricTopol) January 17, 2023

The Great Escape by XBB.1

Erasmus Medical Center Research, Rotterdam

Shows how new versions of the virus evade antibodies generated by previous versions, as well as vaccines

The graph shows the accumulated mutations on various parts of the peak protein

1/3 https://t.co/T9aRY0NYBE pic.twitter.com/eM9nWPY8R5

—Rajeev Jayadevan (@RajeevJayadevan) January 17, 2023