# Prospective Biomarkers of SARS-CoV-2 Vaccine Seroconversion in Patients with Haematological Malignancies

## TL;DR

This study identifies biomarkers that predict whether patients with blood cancers will respond to SARS-CoV-2 vaccines, helping to identify those who may need alternative protection strategies.

## Contribution

The study introduces CXCL13 and CRTAM as novel biomarkers for predicting vaccine response in hematological malignancy patients.

## Key findings

- 37.5% of hematological malignancy patients failed to seroconvert after SARS-CoV-2 vaccination.
- Low levels of CXCL13 and CRTAM were associated with poor vaccine response.
- Non-responders showed dysfunctional T-cell responses to SARS-CoV-2.

## Abstract

Background: SARS-CoV-2 vaccination is crucial for protecting against severe COVID-19 disease; however, patients with haematological malignancies (HM) respond poorly to vaccination due to immunosuppression driven by chemotherapy, targeted cell depletion, and immune dysregulation. We sought to define novel biomarkers that predict effective vaccination in patients with HM. Methods: HM patients and healthy controls received SARS-CoV-2 vaccines and were followed for six months post-vaccination. Virus-specific humoral and cellular immune responses were analysed in serum and whole blood pre- and post-vaccination, and serum proteomics was analysed pre-vaccination to identify potential biomarkers for vaccine response. Results: HM patients displayed delayed antibody seroconversion, and 37.5% failed to seroconvert. Baseline proteomic and cellular immune profiles revealed that T-cell-associated chemokines CXCL13 and CRTAM were differentially expressed, with decreased levels seen in vaccine non-responders. Vaccine response was also associated with a reduced frequency of circulating monocytes, greater numbers of B-cells, and a trend toward greater numbers of CD4+ helper cell phenotypes, including T peripheral helper cells pre-vaccination. In vitro generation of COVID-19-specific T-cells from a subset of participants trended towards increased cytotoxic CD4+ and CD8+ T-cell activity in seroconverters and dysfunctional COVID-19-specific T-cell responses in non-seroconverters. Conclusions: These results suggest that HM patients have impaired T-cell immunity, and non-responders may be identified by low levels of serum CXCL13 and CRTAM. This allows for the identification of at-risk patients who would benefit from alternative COVID-19 prophylaxis strategies.