Enhanced SARS-CoV-2 humoral immunity following breakthrough infection builds upon the preexisting memory B cell pool

Weber, Timm; Dähling, Sabrina; Rose, Svea; Affeldt, Patrick; Vanshylla, Kanika; Ullrich, Leon; Gieselmann, Lutz; Teipel, Finn; Gruell, Henning; Di Cristanziano, Veronica; Kim, Dae Sung; Georgiou, George; Koch, Manuel; Kreer, Christoph; Klein, Florian

doi:10.1126/sciimmunol.adk5845

Cited by 19 publications

(5 citation statements)

References 51 publications

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“…4B and S7B). Such backboosting from a new antigen, which has been shown previously by others 31,39,40 , reflects expansion of memory B cells, leading to the production of cross neutralizing antibodies [52][53][54] . In addition, the XBB.1.5 booster increased neutralization titers against the advanced JN.1 variant, though titers were 5-fold lower than against XBB.1.5.…”

Section: Discussionsupporting

confidence: 58%

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

Wang,

Bhushan,

Paz

et al. 2024

Preprint

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Antigenic assessments of SARS-CoV-2 variants inform decisions to update COVID-19 vaccines. Primary infection sera are often used for assessments, but such sera are rare due to population immunity from SARS-CoV-2 infections and COVID-19 vaccinations. Here, we show that neutralization titers and breadth of matched human and hamster pre-Omicron variant primary infection sera correlate well and generate similar antigenic maps. The hamster antigenic map shows modest antigenic drift among XBB sub-lineage variants, with JN.1 and BA.4/BA.5 variants within the XBB cluster, but with five to six-fold antigenic differences between these variants and XBB.1.5. Compared to sera following only ancestral or bivalent COVID-19 vaccinations, or with post-vaccination infections, XBB.1.5 booster sera had the broadest neutralization against XBB sub-lineage variants, although a five-fold titer difference was still observed between JN.1 and XBB.1.5 variants. These findings suggest that antibody coverage of antigenically divergent JN.1 could be improved with a matched vaccine antigen.

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Section: Discussionsupporting

confidence: 58%

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

Wang,

Bhushan,

Paz

et al. 2024

Preprint

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“…Omicron variants or received Omicron booster vaccines demonstrates the induction of immune imprinting by ancestral SARS-CoV-2 (15)(16)(17)(18)(19)(20). Moreover, the imprinted antibody responses display substantially reduced neutralizing activities against later Omicron variants compared with ancestral SARS-CoV-2 and earlier Omicron variants, highlighting that immune imprinting may impede the generation of neutralizing antibodies against future SARS-CoV-2 variants or other related viruses (21).…”

Section: Analysis Of B Cell Responses In Individuals Who Experienced ...mentioning

confidence: 99%

Ancestral SARS-CoV-2 immune imprinting persists on RBD but not NTD after sequential Omicron infections

Wang,

Li,

et al. 2024

Preprint

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SummaryWhether Omicron exposures could overcome ancestral SARS-CoV-2 immune imprinting remains controversial. Here we analyzed B cell responses evoked by sequential Omicron infections in vaccinated and unvaccinated individuals. Plasma neutralizing antibody titers against ancestral SARS-CoV-2 and variants indicate that immune imprinting is not consistently induced by inactivated or recombinant protein vaccines. However, once induced, immune imprinting is not countered by successive Omicron challenges. We compared binding specificities, neutralizing capacities, developing origins and targeting epitopes of monoclonal antibodies from individuals with or without immune imprinting. Although receptor-binding domain (RBD) and N- terminal domain (NTD) of spike are both primary targets for neutralizing antibodies, immune imprinting only shapes antibody responses to RBD by impeding the production of Omicron-specific neutralizing antibodies while facilitating the development of broadly neutralizing antibodies. We propose that immune imprinting can be either neglected by NTD-based vaccines to induce variant-specific antibodies or leveraged by RBD-containing vaccines to induce broadly neutralizing antibodies.HighlightsImmune imprinting is not consistently induced by vaccinationRepeated Omicron infections could not counter immune imprintingImmune imprinting shapes antibody responses to RBD but not NTDImmune imprinting leads to broadly neutralizing antibodies

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“…Omicron breakthrough infections induce efficient anamnestic immune responses that recruit memory T and B cells cross-reactive to the ancestral strain (Addetia et al, 2023; Kared et al., Koutsakos et al, 2022; Painter et al, 2023; Park et al, Wang et al, 2022; Weber et al., Yisimayi et al, 2023). Many unanswered questions remain on how initial SARS-CoV-2 encounters affect the specificity of antibodies elicited against variant viral strains.…”

Section: Introductionmentioning

confidence: 99%

Immunological imprinting shapes the specificity of human antibody responses against SARS-CoV-2 variants

Johnston,

Li,

Painter

et al. 2024

Preprint

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SummaryThe spike glycoprotein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to accumulate substitutions, leading to breakthrough infections of vaccinated individuals and prompting the development of updated booster vaccines. Here, we determined the specificity and functionality of antibody and B cell responses following exposure to BA.5 and XBB variants in individuals who received ancestral SARS-CoV-2 mRNA vaccines. BA.5 exposures elicited antibody responses that primarily targeted epitopes conserved between the BA.5 and ancestral spike, with poor reactivity to the XBB.1.5 variant. XBB exposures also elicited antibody responses that targeted epitopes conserved between the XBB.1.5 and ancestral spike. However, unlike BA.5, a single XBB exposure elicited low levels of XBB.1.5-specific antibodies and B cells in some individuals. Pre-existing cross-reactive B cells and antibodies were correlated with stronger overall responses to XBB but weaker XBB-specific responses, suggesting that baseline immunity influences the activation of variant-specific SARS-CoV-2 responses.HighlightsVariant breakthrough infections boost ancestral cross-reactive antibodies and B cellsFirst and second BA.5 exposures fail to elicit variant-specific antibodies and B cellsXBB infections and monovalent vaccinations elicit XBB.1.5-specific responses in some individualsXBB.1.5-specific responses correlate with low levels of pre-existing humoral immunity

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Enhanced SARS-CoV-2 humoral immunity following breakthrough infection builds upon the preexisting memory B cell pool

Cited by 19 publications

References 51 publications

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

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

Ancestral SARS-CoV-2 immune imprinting persists on RBD but not NTD after sequential Omicron infections

Immunological imprinting shapes the specificity of human antibody responses against SARS-CoV-2 variants

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