Assessment of mRNA SARS CoV-2 vaccine after administration of tixagevimab/cilgavimab, using B cell analysis

These research results were published online in the British Journal of Haematology.

Previously, B-cell receptor (BCR) repertoire analysis has provided gene sequence data of antibodies (B cell receptors), but it was difficult to use this data to evaluate the immunological reactions to specific antigens.

During the repertoire analysis, the team found that the immunological reactions could be evaluated by "sampling over time in the short time period wherein immunity is activated" and "utilizing the BCR gene sequence database for specific antigens."

This analysis is not the conventional analysis using protein level, such as "the measurement of antibody titers using the ELISA method," but an analysis using mRNA level. Therefore, evaluation is possible for samples with extremely elevated antibody titers after prophylactic administration of antibody preparations (proteins).

Detailed information can be derived, such as antibody epitopes expressed in immunological reactions or neutralization activity, if there is additional information in respect of the antibodies used. By utilizing this method to investigate immune responses following the administration of mRNA vaccines, it will be possible to evaluate the functionality of mRNA formulations.

In recent years, genetically-engineered antibody preparations, such as tixagevimab and cilgavimab, have been widely administered as preventative drugs, primarily for cases with compromised immune systems where there is insufficient antibody production after inoculation with mRNA SARS-CoV-2 vaccines.

This procedure avails of "B cell receptor (BCR) repertoire data relating to the activation period of the humoral immunity" and "the database of the BCR sequences binding to the target antigen". The group analyzed how many of all BCR sequences obtained by BCR Repertoire analysis contain antigen-specific BCR sequences in the database. Credit: Yohei Funakoshi

The overtime variations in the number, frequency and clusters of matched SARS-CoV-2 specific sequences after the initial and second vaccine inoculation. Healthy volunteers received the first dose (1) of mRNA SARS-CoV-2 vaccine (monovalent BNT162b2) and the second dose (2) 21 days later. The researchers searched for SARS-CoV-2 specific sequences from the BCR repertoire data after these vaccine inoculations. Modified from journal article. Credit: 2023 British Society for Haematology and John Wiley & Sons Ltd.

A: Tixagevimab/Cilgavimab was administered to cases after umbilical cord blood transplant and were inoculated with the mRNA vaccine thereafter (yellow arrow). The anti-SARS-CoV-2 antibody titer (black line) transitioned to an extremely high titer value after prophylactic antibody administration, but even then the researchers were able to assess the reactions after vaccine inoculation by assessing SARS-CoV-2 specific sequences (Blue line).B: By availing of the neutralization activity data of antibodies in the database, the research group was able to assess the characteristics of the elevated antibodies after vaccine inoculation. Modified from journal article. Credit: 2023 British Society for Haematology and John Wiley & Sons Ltd.

The shama of Quantification of Antigen-specific Antibody Sequence (QASAS). Credit: Yohei Funakoshi