Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history

Wang, Wei; Lusvarghi, Sabrina; Subramanian, Rahul; Epsi, Nusrat J; Wang, Thomas J.; Goguet, Emilie; Fries, Anthony C; Echegaray, Fernando; Vassell, Russell; Coggins, Si’Ana A.; Richard, Stephanie A; Lindholm, David A; Mende, Katrin; Ewers, Evan C; Larson, Derek; Colombo, Rhonda E; Colombo, Christopher; Joseph, Janet O.; Rozman, Julia S; Smith, Alfred G.; Lalani, Tahaniyat; Berjohn, Catherine M; Maves, Ryan C; Jones, Milissa; Mody, Rupal; Huprikar, Nikhil; Livezey, Jeffrey; Saunders, David; Hollis-Perry, Monique; Wang, Gregory; Ganesan, Anuradha; Simons, Mark P.; Broder, Christopher C.; Tribble, David R.; Laing, E.; Agan, Brian K.; Burgess, Timothy; Mitre, Edward; Pollett, Simon; Katzelnick, Leah C.; Weiss, Carol D.

doi:10.1016/j.chom.2022.10.012

Cited by 45 publications

(81 citation statements)

References 45 publications

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“…To our knowledge, the data and cartography we present is unique in having both BA.1 and BA.2 primary infection sera for the resolution of the basic antigenic relationship among BA.1, BA.2 and BA.5 omicron variants based on data from human sera using replication-competent SARS-CoV-2 variant-based assays. The antigenic map we present here and those by others showed the three sub-lineages as antigenically distinct from pre-omicron VoCs and each other, the location of pre-omicron VoCs correspond well between maps 14,15,23,24 . Differences of BA.2 and BA.5 positions relative to the other VoCs might be explained by maps constructed from different serum groups, adding or decreasing map resolution in different areas of antigenic space (Supplementary Materials Map resolution).…”

Section: Discussionsupporting

confidence: 85%

“…Differences of BA.2 and BA.5 positions relative to the other VoCs might be explained by maps constructed from different serum groups, adding or decreasing map resolution in different areas of antigenic space (Supplementary Materials Map resolution). Wang et al did not include BA.2 convalescent sera in their map, which might explain the proximity of BA.2 and BA.4/5 in their map 23 . In the map we present here and that by van der Straten et al, BA.2 appears antigenically more similar to delta than delta to beta 15 To compare magnitude and breadth of neutralization titers in complex serological data we used antibody landscapes.…”

Section: Discussionmentioning

confidence: 95%

“…This methodology allows analyzing complex serological data beyond primary exposures, as more cross-reactive sera will have flatter landscapes than strain-specific firstexposure sera. While this change in cross-neutralization could be visualized in an antigenic map with variants occupying a smaller space 23 , antibody landscapes are necessary to examine titer magnitude and distribution over mapped space. Grouping by exposure history, we found that at least two distant variant encounters increased crossreactivity of neutralizing antibodies to other variants.…”

Section: Resultsmentioning

confidence: 99%

“…Liu et al attribute this to the differences of the two variants at positions 417, 484, and 50125 . While BA.2 shares these substitutions with beta and not with delta, BA.2 and delta have mutation T478K in common which could contribute to detectable delta titers in the BA.2 convalescents and vice versa23 . Wilks et al have shown that different sera exhibit distinct sensitivities to certain spike mutations14 .…”

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confidence: 99%

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BA.2 and BA.5 omicron differ immunologically from both BA.1 omicron and pre-omicron variants

Rössler

Netzl

Knabl³

et al. 2022

Nat Commun

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Several studies have shown that SARS-CoV-2 BA.1 omicron is an immune escape variant. Meanwhile, however, omicron BA.2 and BA.5 became dominant in many countries and replaced BA.1. As both have several mutations compared to BA.1, we analyzed whether BA.2 and BA.5 show further immune escape relative to BA.1. Here, we characterized neutralization profiles against the BA.2 and BA.5 omicron sub-variants in plasma samples from individuals with different history of exposures to infection/vaccination and found that 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 including all Variants of Concern and BA.1, BA.2 and BA.5 omicron sub-variants, showed that all omicron sub-variants are distinct to pre-omicron variants, but that the three omicron variants are also antigenically distinct from each other. The antibody landscapes illustrate that cross-neutralizing antibodies against the current 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 distant variants. 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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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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BA.2 and BA.5 omicron differ immunologically from both BA.1 omicron and pre-omicron variants

Rössler

Netzl

Knabl³

et al. 2022

Nat Commun

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“…Quantifying the antigenic diversity of variants might assist in selecting future vaccine strains. To determine the antigenic relationships between emerging SARS-CoV-2 omicron variants, we and others 1 , 2 , 3 , 4 used antigenic cartography, whereby multidimensional scaling is used to generate antigenic maps in which the positions of antigens and antiserum samples directly correspond to neutralising titres. This method allows for the quantification and visualisation of antigenic properties of different variants simultaneously.…”

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confidence: 99%

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

Mykytyn¹,

Rosu²,

Kok³

et al. 2023

The Lancet Microbe

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Immune escape of BA.2.86 is comparable to XBB subvariants from the plasma of BA.5‐ and BA.5‐XBB‐convalescent subpopulations

Yang,

Wang,

Liang

et al. 2024

Journal of Medical Virology

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The EG.5.1 variant of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) has been prevalent since mid‐July 2023 in the United States and China. The variant BA.2.86 has become a major concern because it is 34 mutations away from the parental variant BA.2 and >30 mutations from XBB.1.5. There is an urgent need to evaluate whether the immunity of the population and current vaccines are protective against EG.5.1 and BA.2.86. Based on a cohort of two breakthrough‐infected groups, the levels of neutralizing antibodies (NAbs) against different subvariants were measured using pseudovirus‐based neutralization assays. XBB.1.5, EG.5.1, and BA.2.86 are comparably immune‐evasive from neutralization by the plasma of individuals recovered from BA.5 infection (BA.5‐convalescent) or XBB.1.9.2/XBB.1.5 infection following BA.5 infection (BA.5‐XBB‐convalescent). NAb levels against EG.5.1 and BA.2.86 subvariants remained >120 geometric mean titers (GMTs) in BA.5‐XBB‐convalescent individuals 2 months postinfection but were <40 GMTs in BA.5‐convalescent individuals. Furthermore, the XBB‐targeting messenger RNA (mRNA) vaccine RQ3033 induced higher levels of NAbs against XBB.1.5, EG.5.1, and BA.2.86 than against BA.5‐XBB infection. The results suggest that BA.2.86 and EG.5.1 are unlikely to cause more severe concerns than the currently circulating XBB subvariants and that the XBB.1.5‐targeting mRNA vaccine tested has promising protection against EG.5.1 and BA.2.86.

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Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history

Cited by 45 publications

References 45 publications

BA.2 and BA.5 omicron differ immunologically from both BA.1 omicron and pre-omicron variants

BA.2 and BA.5 omicron differ immunologically from both BA.1 omicron and pre-omicron variants

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

Immune escape of BA.2.86 is comparable to XBB subvariants from the plasma of BA.5‐ and BA.5‐XBB‐convalescent subpopulations

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