Mapping SARS-CoV-2 antigenic relationships and serological responses

Abstract

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, multiple variants escaping preexisting immunity emerged, causing reinfections of previously exposed individuals. Here, we used antigenic cartography to analyze patterns of cross-reactivity among 21 variants and 15 groups of human sera obtained after primary infection with 10 different variants or after messenger RNA (mRNA)–1273 or mRNA-1273.351 vaccination. We found antigenic differences among pre-Omicron variants caused by substitutions at spike-protein positions 417, 452, 484, and 501. Quantifying changes in response breadth over time and with additional vaccine doses, our results show the largest increase between 4 weeks and >3 months after a second dose. We found changes in immunodominance of different spike regions, depending on the variant an individual was first exposed to, with implications for variant risk assessment and vaccine-strain selection.

Antigenic cartography using hamster sera identifies SARS-CoV-2 JN.1 evasion seen in human XBB.1.5 booster sera

“…Overall, our primary human and hamster maps show comparable orientations and similar topology to other maps created with human and hamster sera 14-17,28,48 . The consistency between human and hamster maps over a two-year span show that hamster sera are a suitable surrogate for creating antigenic maps to surveil SARS-CoV-2 antigenic variation and predict immune escape.…”

“…Building upon antigenic cartography, antibody landscapes have been useful for characterizing neutralization profiles of individuals who have had multiple antigenic exposures 18,26,28,39,48,50 . The height of an accurate antibody landscape can be used to infer antibody titers against variants that were not used in making of the landscape 18 .…”

Cartography of SARS‐CoV‐2 variants based on the susceptibility to therapeutic monoclonal antibodies

“…The antigenic maps of SARS‐CoV‐2 variants were recently reported by using convalescent sera from patients infected with different variants 17–20 . Surprisingly, the phenotypic cartography developed in this study based on the efficacy of monoclonal antibodies corresponds very well with those antigenic maps.…”

Direct comparison of SARS-CoV-2 variant specific neutralizing antibodies in human and hamster sera

“…Mühlemann et al's framework recommends evaluation of antigenic data on four levels: Titer magnitude, titer fold changes, immunodominance patterns, and antigenic cartography (7). Although the controlled nature of our study comes with the limitation that we did not have serum groups available from both species with known immunodominance changes, such as Beta convalescent sera (7,8), and lacked single-exposure sera from diverse variants to construct welltriangulated antigenic maps (Supplementary Figure 2), it allowed for exact comparison of titer magnitude and fold change trends. Our data indicate that titer fold changes in hamster sera correspond well to human sera, and that titers correspond well after adjusting the data for the higher reactivity generally seen in the hamster.…”