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SARS-CoV-2 vaccine responses following CD20-depletion treatment in patients with haematological and rheumatological disease: a West Midlands Research Consortium study.

ABSTRACT: B-cell-depleting agents are among the most commonly used drugs to treat haemato-oncological and autoimmune diseases. They rapidly induce a state of peripheral B-cell aplasia with the potential to interfere with nascent vaccine responses, particularly to novel antigens. We have examined the relationship between B-cell reconstitution and SARS-CoV-2 vaccine responses in two cohorts of patients previously exposed to B-cell-depleting agents: a cohort of patients treated for haematological B-cell malignancy and another treated for rheumatological disease. B-cell depletion severely impairs vaccine responsiveness in the first 6 months after administration: SARS-CoV-2 antibody seroprevalence was 42.2% and 33.3% in the haemato-oncological patients and rheumatology patients, respectively and 22.7% in patients vaccinated while actively receiving anti-lymphoma chemotherapy. After the first 6 months, vaccine responsiveness significantly improved during early B-cell reconstitution; however, the kinetics of reconstitution was significantly faster in haemato-oncology patients. The AstraZeneca ChAdOx1 nCoV-19 vaccine and the Pfizer BioNTech 162b vaccine induced equivalent vaccine responses; however, shorter intervals between vaccine doses (<1 m) improved the magnitude of the antibody response in haeamto-oncology patients. In a subgroup of haemato-oncology patients, with historic exposure to B-cell-depleting agents (>36 m previously), vaccine non-responsiveness was independent of peripheral B-cell reconstitution. The findings have important implications for primary vaccination and booster vaccination strategies in individuals clinically vulnerable to SARS-CoV-2.

SUBMITTER: Shields AM

PROVIDER: S-EPMC8767851 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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SARS-CoV-2 vaccine responses following CD20-depletion treatment in patients with haematological and rheumatological disease: a West Midlands Research Consortium study.

Shields Adrian M AM Venkatachalam Srinivasan S Shafeek Salim S Paneesha Shankara S Ford Mark M Sheeran Tom T Kelly Melanie M Qureshi Iman I Salhan Beena B Karim Farheen F De Silva Neelakshi N Stones Jacqueline J Lee Sophie S Khawaja Jahanzeb J Kaudlay Praveen Kumar PK Whitmill Richard R Kakepoto Ghulam Nabi GN Parry Helen M HM Moss Paul P Faustini Sian E SE Richter Alex G AG Drayson Mark T MT Basu Supratik S

Clinical and experimental immunology 20220101 1

B-cell-depleting agents are among the most commonly used drugs to treat haemato-oncological and autoimmune diseases. They rapidly induce a state of peripheral B-cell aplasia with the potential to interfere with nascent vaccine responses, particularly to novel antigens. We have examined the relationship between B-cell reconstitution and SARS-CoV-2 vaccine responses in two cohorts of patients previously exposed to B-cell-depleting agents: a cohort of patients treated for haematological B-cell mali ...[more]

PMID: 35020852

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Project description:Background Increasingly junior doctors are taking a year out of the traditional training pathway, and some opt to spend a year in a clinical teaching fellow (CTF) post. The CTF post mainly involves delivering hospital-based teaching to undergraduate medical students. In NHS hospital Trusts in the West Midlands, Heads of Academy (HoAs) have oversight of medical education at each Trust and therefore have responsibility for employing and directing the work of CTFs. Currently, only limited literature exists about the CTF role and exploring this from the point of view of different stakeholders in medical education is important in terms of contributing towards development of the role. This study aimed to explore the views of HoAs in the West Midlands region regarding CTFs employed at their Trusts. Methods All HoAs at the NHS Trust/teaching hospitals associated with the University of Birmingham were invited to take part in an in-depth interview about CTFs at their Trusts. Interviews were held via Zoom recorded using Zoom’s recording functionality. Interview transcripts were then coded and analysed using thematic analysis. Results Seven out of 11 HoAs participated in an interview. Seven themes were identified: CTF duties/Job role, Relationship with students, Benefits of having CTFs, Challenges associated with CTFs, Popularity of the role, What Trust offers CTFs, and Future of the role. Primarily it was felt that having CTFs at their Trust was beneficial in terms of the amount of teaching they provide for medical students. The HoAs were keen to ensure the CTF posts were of maximum benefit to both the post holders and to the Trusts where they were based. The CTF role is one that they felt would continue and develop in the future. Conclusion This study has provided the first insight into the CTF role from the point of view of senior doctors with responsibility for delivery of undergraduate medical education. The consistency and reliability of teaching provided by the CTFs was identified as a key benefit of the role. Future work exploring the role from the point of view of post holders themselves would be beneficial to contribute to development of the role. Supplementary Information The online version contains supplementary material available at 10.1186/s12909-023-04219-y.

Project description:BackgroundClinical trials evaluating anti-CD20-mediated B-cell depletion in multiple sclerosis (MS) and neuromyelitis optica (NMO) generated encouraging results. Our recent studies in the MS model experimental autoimmune encephalomyelitis (EAE) attributed clinical benefit to extinction of activated B-cells, but cautioned that depletion of naïve B-cells may be undesirable. We elucidated the regulatory role of un-activated B-cells in EAE and investigated whether anti-CD20 may collaterally diminish regulatory B-cell properties in treatment of neuroimmunological disorders.MethodsMyelin oligodendrocyte glycoprotein (MOG) peptide-immunized C57Bl/6 mice were depleted of B-cells. Functional consequences for regulatory T-cells (Treg) and cytokine production of CD11b+ antigen presenting cells (APC) were assessed. Peripheral blood mononuclear cells from 22 patients receiving anti-CD20 and 23 untreated neuroimmunological patients were evaluated for frequencies of B-cells, T-cells and monocytes; monocytic reactivity was determined by TNF-production and expression of signalling lymphocytic activation molecule (SLAM).ResultsWe observed that EAE-exacerbation upon depletion of un-activated B-cells closely correlated with an enhanced production of pro-inflammatory TNF by CD11b+ APC. Paralleling this pre-clinical finding, anti-CD20 treatment of human neuroimmunological disorders increased the relative frequency of monocytes and accentuated pro-inflammatory monocyte function; when reactivated ex vivo, a higher frequency of monocytes from B-cell depleted patients produced TNF and expressed the activation marker SLAM.ConclusionsThese data suggest that in neuroimmunological disorders, pro-inflammatory APC activity is controlled by a subset of B-cells which is eliminated concomitantly upon anti-CD20 treatment. While this observation does not conflict with the general concept of B-cell depletion in human autoimmunity, it implies that its safety and effectiveness may further advance by selectively targeting pathogenic B-cell function.

Dataset Information

SARS-CoV-2 vaccine responses following CD20-depletion treatment in patients with haematological and rheumatological disease: a West Midlands Research Consortium study.

Publications

SARS-CoV-2 vaccine responses following CD20-depletion treatment in patients with haematological and rheumatological disease: a West Midlands Research Consortium study.

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