BA.2 omicron differs immunologically from both BA.1 omicron and pre-omicron variants
Abstract
Background
Several studies have shown that SARS-CoV-2 BA.1 omicron is an immune escape variant and current vaccines and infection with pre-omicron variants provide limited protection against BA.1. Meanwhile, however, omicron BA.2 has become the dominant variant in many countries and has replaced BA.1. As BA.2 has several mutations especially in the receptor binding and the N terminal domain compared to BA.1, we analyzed whether BA.2 shows further immune escape relative to BA.1.
Methods
We characterized neutralization profiles against the new BA.2 omicron variant in plasma samples from a variety of individuals with different numbers of exposures to infection/vaccination, including samples from previously virus-naïve, BA.2 omicron-infected individuals. To illustrate antigenic differences of the two omicron sub-variants and pre-omicron variants we performed antigenic cartography and generated antibody landscapes.
Results
Unvaccinated individuals after a single exposure to BA.2 had limited cross-neutralizing antibodies to pre-omicron variants and to BA.1. Consequently, our antigenic map, which included all Variants of Concern and both BA.1 and BA.2 omicron sub-variants, showed that both omicron sub-variants are distinct to pre-omicron variants, but that the two omicron variant are also antigenically distinct from each other. The antibody landscapes illustrate that cross-neutralizing antibodies against the whole antigenic space, as described in our maps, are generated only after three or more exposures to antigenically close variants but also after two exposures to antigenically distinct variants.
Conclusions
Here, we describe the antigenic space inhabited by the relevant SARS-CoV-2 variants, the understanding of which will have important implications for further vaccine strain adaptations.
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