# Humoral immunity after hematopoietic stem cell transplantation: evaluation by B-cell receptor repertoire analysis

## TL;DR

This study shows that the first vaccination after a stem cell transplant triggers a new immune response, even if the person was previously exposed to the antigen.

## Contribution

The study introduces a novel method to distinguish primary and secondary immune responses after hematopoietic stem cell transplantation.

## Key findings

- Primary SARS-CoV-2 exposure in healthy individuals activated immune responses between 14 to 21 days post-exposure.
- Repeated exposure triggered early immune responses (secondary responses) at 7 days post-exposure.
- HSCT patients with prior antigen exposure showed a primary immune response to their first post-HSCT vaccination.

## Abstract

Immunity acquired before hematopoietic stem cell transplantation (HSCT) may decrease or disappear following HSCT, and it is unclear whether the first vaccination after HSCT in patients with an antigen exposure history before HSCT elicits a primary or secondary immune response. The Quantification of Antigen-Specific Antibody Sequence (QASAS) method enables real-time assessment of responses to SARS-CoV-2 antigen exposure through B-cell receptor (BCR) repertoire analysis. Using this method, we evaluated the disappearance of immunological memory after HSCT. First, in individuals without hematologic disorders, primary SARS-CoV-2 antigen exposure elicited no immune response at 7 days post-exposure but demonstrated activation between 14 to 21 days. In contrast, repeated exposure elicited early responses (secondary immune responses) at 7 days post-exposure. We then enrolled HSCT patients with pre-HSCT SARS-CoV-2 antigen exposure history and collected samples before and after vaccination. Despite prior exposure history, patients receiving their first vaccination after HSCT showed no response around 7 days post-exposure but responded at 14 days. In conclusion, even with pre-HSCT antigen exposure, the first vaccination after HSCT induced a primary immune response. This demonstrates that first vaccination after HSCT should be considered to induce a primary immune response, regardless of previous infection or vaccination history.

The online version contains supplementary material available at 10.1007/s12185-025-04042-9.