New Method Enables Assessment of Immunological Reaction to mRNA SARS-CoV-2 Vaccine

A research team has developed a new method to assess the status of immune responses to specific antigens after administration of tixagevimab/cilgavimab using the B cell receptor (BCR) repertoire, according to findings published in the British Journal of Haematology.

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Genetically engineered antibodies such as tixagevimab/cilgavimab are widely used as preventative drugs, primarily for patients with compromised immune systems with insufficient antibody production after vaccination with mRNA SARS-CoV-2 vaccines. However, this prophylaxis approach is not a complete substitute for vaccination and experts recommend that regular vaccines be administered even in cases where prophylaxis is administered.

In these cases, the immunological reaction is typically assessed after vaccination using antibody measurements in the enzyme-linked immunosorbent assay (ELISA). However, because of significant amounts of antibodies from the prophylaxis approach, immunological reactions after vaccination cannot be accurately measured with the ELISA method, necessitating a new approach focusing on mRNA levels rather than protein levels.

BCR repertoire analysis might be that new approach, according to the investigators. This approach analyzes the sequences of antibodies using mRNA and is an effective method for mRNA-level evaluation; however, there was no well-established assessment method for specific antigen reactions utilizing large repertoire data analysis, investigators noted.

“Because this method analyses post-vaccine response at the mRNA level, it can be used to evaluate post-vaccine response in immunocompromised patients who have received antibody prophylaxis,” the study authors said in a press release.

The investigators conducted sampling over time during the short period when immunity is activated and used the BCR gene sequence database to implement repertoire analysis. They found that it was possible to assess the immunological reactions with respect to specific antigens at the mRNA level, and specifically found that the initial immunity is activated around 2 weeks after vaccination with an mRNA SARS-CoV-2 vaccine.

The investigators performed repertoire analysis at approximately 1 week after vaccination when additional immunity is believed to be activated. According to the study, the sequence information derived from repertoire analysis is extremely robust, making it challenging to assess the immunological reaction with respect to specific antigens.

For that reason, the investigators focused on the fact that a large amount of information on SARS-CoV-2 antibody sequences has already been compiled into various databases around the world. Using these data, they focused on sequences that were reported to bind to a specific antigen or sequences similar to it, and conducted an analysis to evaluate post-vaccination responses.

In practice, the investigators said patients who received recombinant antibodies (tixagevimab/silgavimab) after hematopoietic stem cell transplantation have shown extremely high antibody titers with the ELISA method after administration of antibody drugs. Even with such a large amount of antibody proteins in the body, the research group’s method was able to clearly demonstrate a post-vaccine response.

The research group named their method the “Quantification of antigen-specific antibody sequence” (QASAS) method.

“The QASAS method has various advantages that the conventional ELISA method lacks, and it is considered suitable for assessing a wide range of mRNA formulations that are still under development,” the study authors said in a press release.

Reference

Assessment of immunological reaction to mRNA SARS-CoV-2 vaccine after administration of tixagevimab/cilgavimab, using B cell receptor repertoire analysis. News release. EurekAlert. August 17, 2023. Accessed August 17, 2023. https://www.eurekalert.org/news-releases/998838