Antigenic mapping of emerging SARS-CoV-2 omicron variants BM.1.1.1, BQ.1.1, and XBB.1

Next, we generated an updated antigenic map using all available antiserum samples and viral variants (appendix p 3). In this map, all omicron variants were positioned distantly from the pre-omicron cluster. Omicron BA.5 was positioned within one antigenic unit from BA.2, with an antigenic unit representing a two-fold dilution in neutralisation titrations. All remaining omicron variants were positioned 2·3 to 7·0 antigenic units from each other. Omicron BQ.1.1, BM.1.1.1, and XBB.1 mapped the furthest from the pre-omicron variants. Similar results were observed in a map generated in three dimensions (appendix p 4). The data were well represented in two and three dimensions, with no substantial improvement at a higher number of dimensions (appendix p 5). Two dimensional and three dimensional map distances correlated well with neutralisation titres and overall there was good coordination and accuracy in the placement of the antigens and serum samples. Despite the lower certainty in the positioning of BQ.1.1, BM.1.1.1, and XBB.1, the reactive heterologous serum samples present in the map, which are well spaced, allow for a good approximation of the antigenic position of new variants (without their respective homologous serum samples). We observed that human post-vaccination neutralisation titres reflected the antigenic map, as the largest reduction in neutralising titres compared with the D614G variant is against omicron BQ.1.1, BM.1.1.1, and XBB.1, followed by omicron BA.1, BA.2, and BA.5 to similar levels (appendix p 6).

Our data reveal substantial cross-neutralisation of BA.5 antiserum samples against BQ.1.1 but little cross-neutralisation against XBB.1 and BM.1.1.1. Dzespite the antigenic similarities between BA.5 and BQ.1.1, thus far there is little evidence for increased neutralisation of BQ.1.1 by BA.5 bivalent vaccines, potentially due to immunological imprinting.

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• Kurhade C
• Zou J
• Xia H
• et al.

Low neutralization of SARS-CoV-2 omicron BA.2.75·2, BQ.1.1, and XBB.1 by parental mRNA vaccine or a BA.5-bivalent booster.

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• Park YJ
• Pinto D
• Walls AC
• et al.

Imprinted antibody responses against SARS-CoV-2 omicron sublineages.

In addition, these newly emerging variants do not cluster close to each other, therefore a vaccine based on any of these variants might poorly cross-neutralise new, emerging variants, which could be equally antigenically distant. Continuous mapping of new variants and a greater understanding of the evolutionary trajectory of SARS-CoV-2 could indicate potential vaccine candidates.