SARS-CoV-2 Beta and Delta variants trigger Fc effector function with increased cross-reactivity

dc.contributor.authorRichardson, Simone I.
dc.contributor.authorManamela, Nelia P.
dc.contributor.authorMotsoeneng, Boitumelo M.
dc.contributor.authorKaldine, Haajira
dc.contributor.authorAyres, Frances
dc.contributor.authorMakhado, Zanele
dc.contributor.authorMennen, Mathilda
dc.contributor.authorSkelem, Sango
dc.contributor.authorWilliams, Noleen
dc.contributor.authorSullivan, Nancy J.
dc.contributor.authorMisasi, John
dc.contributor.authorGray, Glenda G.
dc.contributor.authorBekker, Linda‑Gail
dc.contributor.authorUeckermann, Veronica
dc.contributor.authorRossouw, Theresa M.
dc.contributor.authorBoswell, M.T.
dc.contributor.authorNtusi, Ntobeko A.B.
dc.contributor.authorBurgers, Wendy A.
dc.contributor.authorMoore, Penny L.
dc.date.accessioned2023-05-12T12:08:55Z
dc.date.available2023-05-12T12:08:55Z
dc.date.issued2022-02-15
dc.description.abstractSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VOCs) exhibit escape from neutralizing antibodies, causing concern about vaccine effectiveness. However, while non-neutralizing cytotoxic functions of antibodies are associated with improved disease outcome and vaccine protection, Fc effector function escape from VOCs is poorly defined. Furthermore, whether VOCs trigger Fc functions with altered specificity, as has been reported for neutralization, is unknown. Here, we demonstrate that the Beta VOC partially evades Fc effector activity in individuals infected with the original (D614G) variant. However, not all functions are equivalently affected, suggesting differential targeting by antibodies mediating distinct Fc functions. Furthermore, Beta and Delta infection trigger responses with significantly improved Fc cross-reactivity against global VOCs compared with D614G-infected or Ad26.COV2.S-vaccinated individuals. This suggests that, as for neutralization, the infecting spike sequence affects Fc effector function. These data have important implications for vaccine strategies that incorporate VOCs, suggesting these may induce broader Fc effector responses.en_US
dc.description.departmentImmunologyen_US
dc.description.departmentInternal Medicineen_US
dc.description.librarianam2023en_US
dc.description.sponsorshipThe EDCTP2 program of the European Union’s Horizon 2020 program, Wellcome Centre for Infectious Diseases Research in Africa, the SA-MRC, MRC UK, NRF, the Lily and Ernst Hausmann Trust, the South African Research Chairs Initiative of the Department of Science and Innovation and National Research Foundation of South Africa, the SA Medical Research Council SHIP program, the Center for the AIDS Program of Research (CAPRISA) and an L’Oreal/UNESCO Women in Science South Africa Young Talents award.en_US
dc.description.urihttp://www.cell.com/cell-host-microbe/homeen_US
dc.identifier.citationRichardson, S.I, Manamela, N.P., Motsoeneng, B.M. et al. 2022, 'SARS-CoV-2 Beta and Delta variants trigger Fc effector function with increased cross-reactivity', Cell Reports Medicine, vol. 3, art. 100510, pp. 1-8, doi : 10.1016/j.xcrm.2022.100510.en_US
dc.identifier.issn1931-3128 (print)
dc.identifier.issn1934-6069 (online)
dc.identifier.other10.1016/j.xcrm.2022.100510
dc.identifier.urihttp://hdl.handle.net/2263/90658
dc.language.isoenen_US
dc.publisherCell Pressen_US
dc.rights© 2022 Authors. This is an open access article under the CC BY-NC-ND IGO license.en_US
dc.subjectSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)en_US
dc.subjectVaccineen_US
dc.subjectAntibodiesen_US
dc.subjectInfectionen_US
dc.subjectVariants of concern (VOCs)en_US
dc.titleSARS-CoV-2 Beta and Delta variants trigger Fc effector function with increased cross-reactivityen_US
dc.typeArticleen_US

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