Greater preservation of SARS-CoV-2 neutralising antibody responses following the ChAdOx1-S (AZD1222) vaccine compared with mRNA vaccines in haematopoietic cell transplant recipients

Hayley Colton; Natalie Barratt; Nigel Temperton; Hailey Hornsby; Adrienn Angyal; Irina Grouneva; Benjamin B Lindsey; Pamela Kearns; Eleanor Barnes; Carl S Goodyear; Alex Richter; David Thomas; Gordon Cook; Iain B McInnes; Michelle Willicombe; Stefan Siebert; Kim Orchard; Rachael Selby; Sarah Bowden; Paul J Collini; Ann Pope; Amanda Kirkham; Barbara Kronsteiner; Susanna J Dunachie; Paul Miller; Jennifer Clay; Erin Hurst; Ram Malladi; Murali Kesavan; Francesca Kinsella; Robin Sanderson; Kwee L Yong; Daniel Rea; Helen Parry; PITCH Consortium, OCTAVE Collaborative Group, OCTAVE‐DUO Investigators, PROSECO Investigators; Sean H Lim; John A Snowden; Thushan I de Silva

doi:10.1111/bjh.19874

Greater preservation of SARS-CoV-2 neutralising antibody responses following the ChAdOx1-S (AZD1222) vaccine compared with mRNA vaccines in haematopoietic cell transplant recipients

Br J Haematol. 2024 Dec;205(6):2206-2218. doi: 10.1111/bjh.19874. Epub 2024 Nov 17.

Authors

Hayley Colton^{1

2}, Natalie Barratt^{1

2}, Nigel Temperton³, Hailey Hornsby^{1

2}, Adrienn Angyal^{1

2}, Irina Grouneva^{1

2}, Benjamin B Lindsey^{1

2}, Pamela Kearns⁴, Eleanor Barnes⁵, Carl S Goodyear⁶, Alex Richter⁷, David Thomas⁸, Gordon Cook⁹, Iain B McInnes⁶, Michelle Willicombe¹⁰, Stefan Siebert⁶, Kim Orchard¹¹, Rachael Selby¹², Sarah Bowden⁴, Paul J Collini^{1

2}, Ann Pope⁴, Amanda Kirkham⁴, Barbara Kronsteiner⁵, Susanna J Dunachie⁵, Paul Miller¹³, Jennifer Clay¹⁴, Erin Hurst¹⁵, Ram Malladi¹⁶, Murali Kesavan¹⁷, Francesca Kinsella¹⁸, Robin Sanderson¹⁹, Kwee L Yong²⁰, Daniel Rea⁴, Helen Parry¹⁸; PITCH Consortium, OCTAVE Collaborative Group, OCTAVE‐DUO Investigators, PROSECO Investigators; Sean H Lim²¹, John A Snowden^{1

2

12}, Thushan I de Silva^{1

2

12}

Affiliations

¹ Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield, Sheffield, UK.
² NIHR Sheffield Biomedical Research Centre and the Florey Institute of Infection, University of Sheffield, Sheffield, UK.
³ Viral Pseudotype Unit, Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham, UK.
⁴ Cancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham, Birmingham, UK.
⁵ Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
⁶ College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, UK.
⁷ Clinical Immunology Service, University of Birmingham, Birmingham, UK.
⁸ The Cambridge Institute for Therapeutic Immunology and Infectious Disease (CITIID), University of Cambridge, Cambridge, UK.
⁹ National Institute for Health Research, Leeds MIC, University of Leeds, Leeds, UK.
¹⁰ Department of Immunology and Inflammation, Centre for Inflammatory Disease, Imperial College London, London, UK.
¹¹ Department of Haematology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
¹² Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield, UK.
¹³ British Society of Blood and Marrow Transplantation and Cellular Therapy, Guy's Hospital, London, UK.
¹⁴ Department of Haematology, St James's University Hospital, Leeds, UK.
¹⁵ Northern Centre for Cancer Care, Freeman Hospital, Newcastle, UK.
¹⁶ Department of Haematology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
¹⁷ Department of Oncology, Cancer and Haematology Centre, Churchill Hospital, Oxford, UK.
¹⁸ Centre for Clinical Haematology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
¹⁹ King's College Hospital NHS Foundation Trust, London, UK.
²⁰ Department of Haematology, Cancer Institute, University College London, London, UK.
²¹ Centre for Cancer Immunology, University of Southampton, Southampton, UK.

Abstract

Whilst SARS-CoV-2 mRNA vaccines generate high neutralising antibodies (nAb) in most individuals, haematopoietic stem cell transplant (HSCT) and chimeric antigen receptor T-cell (CAR-T) recipients respond poorly. HSCT/CAR-T treatment ablates existing immune memory, with recipients requiring revaccination analogous to being vaccine naive. An optimal revaccination strategy for this cohort has not been defined. Factors predicting immunogenicity following three ancestral SARS-CoV-2 vaccines were assessed in 198 HSCT/CAR-T recipients and 96 healthcare workers (HCWs) recruited to multicentre studies. Only 25% of HSCT/CAR-T recipients generated nAbs following one dose, with titres 167-fold and 7-fold lower than that in HCWs after the first and second doses, respectively. Lower post-second dose nAb titres were associated with older age, rituximab use, and previous HSCT. ChAdOx1-S recipients were more likely to generate nAbs compared with mRNA vaccines, with titres comparable to HCWs. In contrast, nAbs were significantly lower in HSCT/CAR-T recipients than HCWs after mRNA vaccination. The poor first-dose immunogenicity in HSCT/CAR-T recipients suggests a minimum licensed dosing interval could limit the period of vulnerability following HSCT/CAR-T. The relative preservation of nAbs with ChAdOx1-S vaccination highlights the importance of evaluating alternative platforms to mRNA vaccination within this highly vulnerable clinical cohort.

Keywords: SARS‐CoV‐2; stem cell transplant; vaccination.

Publication types

Multicenter Study
Comparative Study

MeSH terms

Adult
Aged
Antibodies, Neutralizing* / blood
Antibodies, Viral* / blood
COVID-19 Vaccines / administration & dosage
COVID-19 Vaccines / immunology
COVID-19* / immunology
COVID-19* / prevention & control
ChAdOx1 nCoV-19* / administration & dosage
Female
Hematopoietic Stem Cell Transplantation*
Humans
Immunization, Secondary
Immunogenicity, Vaccine
Male
Middle Aged
SARS-CoV-2* / immunology
mRNA Vaccines

Substances

Antibodies, Neutralizing
Antibodies, Viral
ChAdOx1 nCoV-19
COVID-19 Vaccines
mRNA Vaccines

Abstract

Publication types

MeSH terms

Substances

Grants and funding