Immunogenicity of Covid-19 vaccination in patients with myelodysplastic syndromes

ABSTRACT

Many patients with haematological cancers remain incompletely protected from SARS-CoV-2 following two doses of vaccine with Pfizer-BioNTech BNT162b2 nCoV-19 or ChAdOx1. Myelodysplastic syndrome (MDS) represents a spectrum of clonal bone marrow neoplasms. The response of patients with MDS to the COVID-19 vaccines remains unknown. Here, we report the humoral and T-cell responses of patients with low-and high-risk myelodysplastic syndrome (MDS), 2 weeks following completion of the second-dose schedules of ChAdOx1 or BNT162b2 nCoV-19 vaccines. Patients with MDS ( n = 38) followed up at Kings College Hospital, London were vaccinated with either BNT162b2 mRNA or ChAdOx1 nCoV-19 vaccine. Written informed consent was provided. Eligibility criteria included the diagnosis of MDS as per the WHO classification and age ≥18 years. Healthy volunteers (HV;n = 30) served as a reference group. Blood samples were collected 2 weeks after the second vaccine dose. Plasma samples were tested for SARS-CoV-2-specific antibody aimed at the SARS-CoV-2 spike (S) protein receptor-binding domain and neutralisation assays against pseudotypes with SARS-CoV-2 Wuhan strain (WT), VOC.B.1.1.7 (alpha) or VOC.B.1.617.2 (delta) Spike. Cellular responses were assessed using IFNγ ELISPOT and flow cytometry (CD25 and CD69 expression) after 24 h peptide stimulation. IFNγ ELISpot analysis was performed ex vivo for assessment of T-cell response. 32% of the MDS patients received BNT162b2 and 58% received ChAdOx1 nCoV-19 vaccines. All HV received BNT162b2. Overall serological responses were as follows HV BNT162b2 100% (26/26);MDS BNT162b2 100% (15/15) and MDS ChAdOx1 76.2% (16/21). Notably, the MDS ChAdOx1 cohort demonstrated significantly decreased serological titres to the MDS BNT162b2 cohort. The functional implications of seroconversion were assessed by neutralisation assays for SARS-CoV-2 WT and VOC alpha and delta. All but four MDS patients could neutralise all variant strains, but MDS cohorts showed significantly reduced median neutralisations for all three variant strains compared to HV. Five MDS ChAdOx1 patients who did not have a serological response were able to mount T-cell responses. Additionally, treatment with either azacytidine or calcineurin inhibitor cyclosporin did not impair appropriate T-cell responses. The numbers of individuals who were both serological and T-cell responders were as follows HV 95% (20/21), MDS BNT162b2 71.4% (10/14) and MDS ChAdOx1 52.9% (9/17). Overall serological responses in the MDS cohorts were 100% for those who had completed the two-dose BNT162b2 vaccine schedule compared to 76.2% of patients vaccinated with the ChAdOx1 vaccine. It may be advisable that MDS patients are boosted with an mRNA-based vaccine to promote enhanced immunity in this specific population. We observed that neutralisation in seroconverted patients was significantly weaker for both the ChAdOx-1 and BNT162b2 MDS cohorts compared to HV. This highlights the continued need for a third primary dose for this clinically vulnerable patient group and our further work will analyse the cohort's response to this.