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Low Frequency of T Cell and Antibody Responses to Vaccination Against Sars-Cov-2 in Patients Post Allogeneic Stem Cell Transplantation in Comparison with Chronic Myeloid Malignancy Patients
Blood ; 138:3920, 2021.
Article in English | EMBASE | ID: covidwho-1582225
ABSTRACT

Introduction:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to unprecedented healthcare challenges on a global scale. Impressive efforts have led to rapid development of multiple efficacious vaccines against SARS-CoV-2, however concerns remain over the degree of protection vaccination offers to immunocompromised recipients. To answer this question, we have designed a prospective study to evaluate response to vaccination in patients with haematological malignancies (Harrington, Leukaemia 2021;Harrington, BJHaem, 2021). 103 patients were included with samples collected in 60 patients after first dose and 71 patients following second dose. We have analysed humoral and T cell response to a first dose of vaccine against SARS-CoV-2 in patients post allogeneic stem cell transplantation (HSCT) and compared those to patients with CML or MPN.

Methods:

ELISA plates were coated with antigen Nuclear (N) protein or the S protein. Serial dilutions of plasma were added to wells and incubated for 2 h at room temperature. Control reagents included N-specific monoclonal antibody, S-specific monoclonal antibody, negative control plasma, positive control plasma and blank wells. Secondary antibody was added and incubated for 1h at room temperature. IgG was detected using goat-anti-human-Fc-AP and plates read at 405 nm. Where an EC50 was not reached at 125, a plasma was considered seropositive if the OD at 405nm was 4-fold above background and a value of 25 was assigned. T cell functionality was assessed using intracellular cytokine staining after incubation with SARS-CoV-2 specific peptides covering immunogenic domains of the Spike (S) protein. A response was considered positive if there was a 3-fold increase in pro-inflammatory cytokine expression from baseline, and above a threshold of 0.01. Specific peptides (0.25 µg/ml), anti-CD28 and BFA were added to cells. Unstimulated cells were utilised as negative controls. Cells were stained with viability dye, then with antibodies directed against surface markers, and fixed and permeabilised prior to staining for intracellular cytokines TNFa and IFNg. Gating on lymphocytes, single cells, live cells, CD3+ cells, CD4+ cells and CD4- (CD8+) was performed.

Results:

Of the 103 patients included in this study, post vaccination evaluation on 56 patients have been analysed so far, including 37 patients with chronic myeloid malignancies (MPN n=21 and CML n=16) and 19 patients post HSCT. From the latter group, median time since transplant was 53.9 months (18.7 to 76.8) with 12 participants on extracorporeal photopheresis (ECP) therapy for graft versus host disease (GvHD) with median frequency of 24.5 days (14-42). BNT162b2 vaccine was administered to 48 patients (85.7%). An anti-S IgG response was observed after a first dose in 16/21 (76.1%) of the MPN group and 14/16 (87.5%) of CML patients, but in only 7/19 (36.8%) of post HSCT patients (Fishers Exact Test - p=0.02/0.002, Fig 1a). Of the latter group a low positive value where an EC50 was not reached was observed in 4/19 (21.1%) and a moderate response in 3/19 patients (15.8%). Of the 12 patients with active GvHD on ECP, a positive response was observed in 4 patients (33.3%), however only one patient recorded a response where an EC50 was measurable. A T cell response was observed in 16/20 (80%) of the MPN group and 14/15 (93.3%) of those with CML after a single dose, with a polyfunctional T cell response (>1 cytokine) observed in 65% and 80% respectively. In comparison only 5/19 patients (38.5%) post HSCT mounted a T cell response (p=0.027/p=0.002, Fig 1b), with a CD4+ response in 4 (30.8%) and a CD8+ response in 3 (23.1%). In this group, a polyfunctional T cell response was found in 4/19 patients (30.8%). 33.3% of patients with GVHD requiring ECP had a T cell response, compared with 42.9% in post HSCT without GVHD.

Summary:

Despite encouraging results of antibody and T cell response to a first vaccination dose in patients with chronic myeloid malignancies, these results raise concerns regarding the humoral and T cell respo ses to vaccination in patients post HSCT, recognised as a particularly immunosuppressed group. Further longitudinal data is required to determine if these results translate into a reduction in cases and severity of infection in these groups. We are currently analysing the response to a second vaccine injection and responses to sequential doses of vaccination across the whole cohort will be presented. [Formula presented] Disclosures Harrington Bristol Myers Squibb Research Funding;Incyte Honoraria. Radia Blueprint Medicines Corporation Consultancy, Membership on an entity's Board of Directors or advisory committees, Other Study steering group member, Research Funding;Novartis Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other Education events;Cogent Biosciences Incorporated Other Study Steering Committee;EXPLORER and PATHFINDER studies Other Member of the Response Adjudication Committee. Kordasti Beckman Coulter Honoraria;Celgene Research Funding;Novartis Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Alexion Honoraria. Dillon Menarini Membership on an entity's Board of Directors or advisory committees;Novartis Membership on an entity's Board of Directors or advisory committees, Other Session chair (paid to institution), Speakers Bureau;Astellas Consultancy, Other Educational Events, Speakers Bureau;Abbvie Consultancy, Membership on an entity's Board of Directors or advisory committees, Other Research Support, Educational Events;Amgen Other Research support (paid to institution);Pfizer Consultancy, Membership on an entity's Board of Directors or advisory committees, Other educational events;Jazz Other Education events;Shattuck Labs Membership on an entity's Board of Directors or advisory committees. Harrison Promedior Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;AOP Orphan Pharmaceuticals Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Incyte Corporation Speakers Bureau;Gilead Sciences Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Constellation Pharmaceuticals Research Funding;Galacteo Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Geron Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;BMS Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Celgene Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Abbvie Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Sierra Oncology Honoraria;Roche Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Janssen Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Shire Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;CTI BioPharma Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Keros Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. de Lavallade Bristol Myers Squibb Research Funding;Incyte Honoraria, Research Funding;Novartis Speakers Bureau.
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Full text: Available Collection: Databases of international organizations Database: EMBASE Topics: Vaccines Language: English Journal: Blood Year: 2021 Document Type: Article

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Full text: Available Collection: Databases of international organizations Database: EMBASE Topics: Vaccines Language: English Journal: Blood Year: 2021 Document Type: Article