Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer

Fendler, Annika; Shepherd, Scott TC; Au, Lewis; Wu, Mary; Harvey, Ruth; Wilkinson, Katalin A; Schmitt, Andreas M; Tippu, Zayd; Shum, Benjamin; Farag, Sheima; Rogiers, Aljosja; Carlyle, Eleanor; Edmonds, Kim; Del Rosario, Lyra; Lingard, Karla; Mangwende, Mary; Holt, Lucy; Ahmod, Hamid; Korteweg, Justine; Foley, Tara; Barber, Taja; Emslie-Henry, Andrea; Caulfield-Lynch, Niamh; Byrne, Fiona; Deng, Daqi; Kjaer, Svend; Song, Ok-Ryul; Queval, Christophe J; Kavanagh, Caitlin; Wall, Emma C; Carr, Edward J; Caidan, Simon; Gavrielides, Mike; MacRae, James I; Kelly, Gavin; Peat, Kema; Kelly, Denise; Murra, Aida; Kelly, Kayleigh; O’Flaherty, Molly; Shea, Robyn L; Gardner, Gail; Murray, Darren; Popat, Sanjay; Yousaf, Nadia; Jhanji, Shaman; Tatham, Kate; Cunningham, David; Van As, Nicholas; Young, Kate; Furness, Andrew JS; Pickering, Lisa; Beale, Rupert; Swanton, Charles; Gandhi, Sonia; Gamblin, Steve; Bauer, David LV; Kassiotis, George; Howell, Michael; Nicholson, Emma; Walker, Susanna; Wilkinson, Robert J; Larkin, James; Turajlic, Samra

doi:10.25418/crick.21370617.v1

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Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer

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posted on 2022-10-20, 13:02 authored by Annika Fendler, Scott TC Shepherd, Lewis Au, Mary Wu, Ruth Harvey, Katalin A Wilkinson, Andreas M Schmitt, Zayd Tippu, Benjamin Shum, Sheima Farag, Aljosja Rogiers, Eleanor Carlyle, Kim Edmonds, Lyra Del Rosario, Karla Lingard, Mary Mangwende, Lucy Holt, Hamid Ahmod, Justine Korteweg, Tara Foley, Taja Barber, Andrea Emslie-Henry, Niamh Caulfield-Lynch, Fiona Byrne, Daqi Deng, Svend Kjaer, Ok-Ryul Song, Christophe J Queval, Caitlin Kavanagh, Emma C Wall, Edward J Carr, Simon Caidan, Mike Gavrielides, James I MacRae, Gavin Kelly, Kema Peat, Denise Kelly, Aida Murra, Kayleigh Kelly, Molly O’Flaherty, Robyn L Shea, Gail Gardner, Darren Murray, Sanjay Popat, Nadia Yousaf, Shaman Jhanji, Kate Tatham, David Cunningham, Nicholas Van As, Kate Young, Andrew JS Furness, Lisa Pickering, Rupert Beale, Charles Swanton, Sonia Gandhi, Steve Gamblin, David LV Bauer, George Kassiotis, Michael Howell, Emma Nicholson, Susanna Walker, Robert J Wilkinson, James Larkin, Samra Turajlic

Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886) we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralising antibody titres (NAbT) using a live virus microneutralization assay against wild-type (WT), Delta, Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titres and T cell responses after the fourth vaccine dose increases compared to those after the third vaccine dose. Patients who received B cell-depleting therapies within 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination.

Funding

Crick (Grant ID: 11104, Grant title: Bauer FC011104) Crick (Grant ID: 10827, Grant title: Beale FC001827) Crick (Grant ID: 10078, Grant title: Gamblin FC001078) Crick (Grant ID: 10099, Grant title: Kassiotis FC001099) Crick (Grant ID: CC1107, Grant title: STP Bioinformatics & Biostatistics) Crick (Grant ID: CC1071, Grant title: STP High Throughput Screening) Crick (Grant ID: CC1067, Grant title: STP Metabolomics) Crick (Grant ID: CC1119, Grant title: STP Scientific Computing) Crick (Grant ID: CC1068, Grant title: STP Structural Biology) Crick (Grant ID: 10169, Grant title: Swanton FC001169) Crick (Grant ID: 10988, Grant title: Turajlic FC001988) Crick (Grant ID: 10218, Grant title: Wilkinson, R FC001218) Cancer Research UK (Grant ID: 18176, Grant title: CRUK C50947/A18176) Rosetrees Trust (Grant ID: M926, Grant title: RT M926) Novo Nordisk UK Research Foundation (Grant ID: NNF15OC0016584, Grant title: NovoNordisk Foundation 16584) European Research Council (Grant ID: 835297 - PROTEUS, Grant title: ERC 835297 - PROTEUS)

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https://doi.org/10.1016/j.xcrm.2022.100781

Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer

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