Response to mRNA SARS‐CoV‐2 vaccination evaluated by B‐cell receptor repertoire after tixagevimab/cilgavimab administration

Abstract

Summary The use of anti‐SARS‐CoV‐2 antibody products like tixagevimab/cilgavimab represents an important strategy to protect immunocompromised patients with haematological malignancies from COVID‐19. Although patients who receive these agents should still be vaccinated, the use of tixagevimab/cilgavimab can mask the production of anti‐spike antibody after vaccination, making it hard to assess vaccine response. We have newly established a quantification method to assess the response to SARS‐CoV‐2 vaccination at the mRNA level using B‐cell receptor (BCR) repertoire assay and the Coronavirus Antibody Database (CoV‐AbDab). Repeated blood samples before and after vaccination were analysed for the BCR repertoire, and BCR sequences were searched in the database. We analysed the number and percentage frequency of matched sequences. We found that the number of matched sequences increased 2 weeks after the first vaccination and quickly decreased. Meanwhile, the number of matched sequences more rapidly increased after the second vaccination. These results show that the postvaccine immune response can be assessed at the mRNA level by analysing the fluctuation in matching sequences. Finally, BCR repertoire analysis with CoV‐AbDab clearly demonstrated the response to mRNA SARS‐CoV‐2 vaccination even after tixagevimab/cilgavimab administration in haematological malignancy patients who underwent allogeneic haematopoietic stem cell transplantation.

Analysis of B-cell receptor repertoire to evaluate immunogenicity of monovalent Omicron XBB.1.5 mRNA vaccines

“…In our previous research, we evaluated the immune response in individuals primed with previous vaccines or SARS-CoV-2 infection through the QASAS method. 11 These included three cases of SARS-CoV-2 infection in early 2020 and six cases of individuals who had received previous vaccines (monovalent original mRNA vaccines and bivalent original/Omicron BA.4/5 mRNA vaccine). These nine cases were treated as a cohort exposed to antigens before the appearance of the Omicron XBB sublineage (Supplementary Table 1).…”

“…Furthermore, compared to conventional tests, which detect antibodies with a long half-life, the QASAS method directly detects BCR mRNA as short-lived as B cell activity, making it possible for our method to monitor the real-time activity of humoral immunity. Given that the initial vaccine immunization in our previous study took two weeks to increase the SARS-CoV- 2-specific BCR/antibody sequences, 11 we consider that the rapid peak in B-cell activation after antigen exposure indicates the effect of a boosted immune response.…”

“…Sequences detected in BCR repertoire analysis of PBMCs from vaccinated patients were searched against the classified reference sequence, and sequences with CDR3 amino acid sequence exact match (Levenshtein distance 0, LV0) or 1 amino acid mismatch (LV1) were counted. 11…”

“…Previously, we established a new method to assess the response to SARS-CoV-2 vaccination at the mRNA level by quantifying antigen-specific antibody sequences, named the “Quantification of Antigen-specific Antibody Sequence (QASAS) method”. 11 This method uses B-cell receptor (BCR) repertoire data on activation of humoral immunity and a database of BCR sequences that bind to target antigens, such as the Coronavirus Antibody Database (CoV-AbDab). 12 Since the CoV-AbDab contains information on variants to which each antibody sequence binds, our method allows us to infer the antigen specificity of antibody sequences generated by the vaccine.…”

Comprehensive procedure for injecting Evusheld® for hematological diseases in a single institute

“…Passive monoclonal antibodies for COVID-19 prophylaxis were indicated among the high-risk, more vulnerable population such as those immunocompromised. EVA was approved only for immunocompromised patients undergoing cancer chemotherapy, including rituximab, hematopoietic stem cell transplantation, and CAR-T [5,6]. We experienced long-lasting COVID-19 reactivation [7], also known as long COVID [8].…”