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

Antigenic characterization of newly emerging SARS-CoV-2 variants is important to assess their immune escape and judge the need for future vaccine updates. As exposure histories for human sera become more and more complex, animal sera may provide an alternative for antigenic characterization of new variants. To bridge data obtained from animal sera with human sera, we here analyzed neutralizing antibody titers in human and hamster first infection sera in a highly controlled setting using the same live-virus neutralization assay performed in one laboratory. Using a Bayesian framework, we found that titer fold changes in hamster sera corresponded well to human sera and that hamster sera generally exhibited higher reactivity. Our results indicate that sera from infected hamsters are a good surrogate for the antigenic characterization of new variants.

Characterizing SARS-CoV-2 neutralization profiles after bivalent boosting using antigenic cartography (preprint)

Since emergence of the initial SARS-CoV-2 omicron BA.1, BA.2 and BA.5 variants, omicron has diversified substantially. Antigenic characterization of these new variants is important to analyze their potential immune escape from population immunity and implications for future vaccine composition. Here, we describe an antigenic map based on human single-exposure sera and live-virus isolates that includes a broad selection of recently emerged omicron variants such as BA.2.75, BF.7, BQ, XBB and XBF variants. Recent omicron variants clustered around BA.1 and BA.5 with some variants further extending the antigenic space. Based on this antigenic map we constructed antibody landscapes to describe neutralization profiles after booster immunization with bivalent mRNA vaccines based on ancestral virus and either BA.1 or BA.4/5 omicron. Immune escape of BA.2.75, BQ, XBB and XBF variants was also evident in bivalently boosted individuals, however, cross-neutralization was improved for those with hybrid immunity. Our results indicate that future vaccine updates are needed to induce cross-neutralizing antibodies against currently circulating variants. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/23289412v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@16819e7org.highwire.dtl.DTLVardef@17c9bc6org.highwire.dtl.DTLVardef@1d6f349org.highwire.dtl.DTLVardef@fe6ec7_HPS_FORMAT_FIGEXP M_FIG C_FIG

BA.2 omicron differs immunologically from both BA.1 omicron and pre-omicron variants (preprint)

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-naive, 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.

Mapping SARS-CoV-2 antigenic relationships and serological responses (preprint)

During the SARS-CoV-2 pandemic, multiple variants with differing amounts of escape from pre-existing immunity have emerged, causing concerns about continued protection. Here, we use antigenic cartography to quantify and visualize the antigenic relationships among 16 SARS-CoV-2 variants titrated against serum samples taken post-vaccination and post-infection with seven different variants. We find major antigenic differences caused by substitutions at positions 417, 452, 484, and possibly 501. B.1.1.529 (Omicron) showed the highest escape from all sera tested. Visualization of serological responses as antibody landscapes shows how reactivity clusters in different regions of antigenic space. We find changes in immunodominance of different spike regions depending on the variant an individual was exposed to, with implications for variant risk assessment and vaccine strain selection.

Analysis of SARS-CoV-2 Omicron Neutralization Data up to 2021-12-22 (preprint)

The rapid spread of the Omicron SARS-CoV-2 variant (B.1.1.529) resulted in international efforts to quickly assess its escape from immunity generated by vaccines and previous infections. Numerous laboratories published Omicron neutralization data as preprints and reports. The understandable limitations and variability in such rapid reporting of early results however made it difficult to make definitive statements about the data. Here, we aggregate and analyze Omicron neutralization data from 23 reporting laboratories up to 2021-12-22. There are enough data to identify multiple trends and make two definitive points. First, in twice-vaccinated individuals, titer fold drop of Omicron relative to wild type is more than 19x, likely substantially more given the number of measurements below the limit of detection of the assay. Second, out to one month post third vaccination with an mRNA vaccine, or twice vaccinated after an earlier infection, the titer fold drop to Omicron is substantially less at approximately 7x. This substantially lower fold drop and somewhat higher titers after 3rd vaccination are strong early evidence for the utility of booster vaccination.