Humoral and T-cell responses to SARS-CoV-2 vaccination in myeloproliferative neoplasm patients

In this study we evaluated myeloproliferative neoplasm patients' serologic and T-cell responses 1 month after SARS-CoV-2 vaccination. While response rates were overall high, subtle deficiencies in T-cell responses likely indicate some impaired cellular immunity that requires further investigation.
Published in Cancer
Like

Myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET), polycythemia vera (PV), myelofibrosis (MF), and chronic myeloid leukemia (CML) are chronic leukemias characterized by immune dysregulation. As a result, infections are a leading cause of morbidity and mortality, and patients are at high risk of complications from COVID-19. BNT162b2 (Pfizer/BioNTech) and mRNA-1273 (Moderna) are SARS-CoV-2 mRNA vaccines are highly effective in preventing severe COVID-19 in healthy populations, but their efficacy in MPN patients is overall unclear.

We therefore investigated humoral and T-cell responses after SARS-CoV-2 vaccination in MPN patients. Although most reports of SARS-CoV-2 immunogenicity have focused on quantifying anti-spike antibodies in peripheral blood, T-cell responses are an essential component of the anti-viral immune response against SARS-CoV-19, especially in the prevention of severe COVID-19 caused by emerging variants such as Omicron. In addition to serologic measurements against the SARS-CoV-2 spike protein, we utilized two IFNγ-release assays, the ELISpot and whole blood assay previously developed in convalescent and vaccinated healthy individuals, to assess T-cell responses in MPN patients 1 month after vaccination.

A total of 28 MPN patients were enrolled in the study, and we also included vaccination response data from 26 healthy donors as controls. We measured qualitative total IgG/IgM/IgA against the SARS-CoV-2 spike protein and found 96% serologic response rates in MPN patients. However, quantitative IgG anti-spike testing demonstrated a trend toward lower median post-vaccination binding antibody units (BAU) in MPN patients compared to healthy donors.

MPN patients also demonstrated high rates of T-cell responses on ELISpot testing. Overall, 93% of MPN patients had a positive ELISpot after vaccination, which was similar to healthy controls. However, MPN patients had significantly lower median spot-forming units (SFUs) on ELISpot testing compared to healthy donors. MF patients tended to have lower ELISpot SFUs, although this was not significant in within-group comparisons. In an effort to develop a T-cell response assay that required less intensive processing than the ELISpot assay, a whole-blood assay based on the in vitro diagnostic QuantiFERON TB Gold Plus assay was also used to assess T-cell response. Unlike ELISPot results, MPN patients had significantly lower T-cell responses on whole blood testing compared to healthy controls (54% vs 100%, p=0.002).

MPN patients were significantly older compared to healthy controls, and we did find that older age was associated with lower T-cell responses on ELISPot and whole blood testing, although age was not associated with serologic responses. In multivariable analysis, an MPN diagnosis was no longer associated with lower SFUs on ELISpot testing when accounting for age, suggesting that older age was likely a confounding effect. However, older age was no longer significantly associated with T-cell responses on whole blood testing when accounting for an MPN diagnosis in multivariable analysis. We found no other effects on antibody or T-cell responses by vaccine type, gender, treatment, absolute lymphocyte count, or number of days post-vaccine.

Although we found >90% serologic and T-cell responses in MPN patients after vaccination, our study also provides evidence for decreased cellular immunity in MPN patients. MPN patients had lower overall magnitude T-cell responses compared to healthy donors, and there were discrepancies in T-cell responses between assays that were present in MPN patients but not healthy donors. MF patients likely have the worse responses within MPN patients, although are sample size was too limited to detect a significant effect. Our study is limited by the relatively small and heterogenous sample. Age is also a confounding effect, but the results of our multivariable analysis suggests that it does not account for all the differences in immune responses. Given the importance of T-cell responses in preventing severe COVID-19, the cellular impairments detected in our investigation remain an area of active investigation.

Please sign in or register for FREE

If you are a registered user on Research Communities by Springer Nature, please sign in

Subscribe to the Topic

Cancer Biology
Life Sciences > Biological Sciences > Cancer Biology
  • Leukemia Leukemia

    This journal publishes high quality, peer reviewed research that covers all aspects of the research and treatment of leukemia and allied diseases. Topics of interest include oncogenes, growth factors, stem cells, leukemia genomics, cell cycle, signal transduction and molecular targets for therapy.