Cigolini, B. | Search bioRxiv

bioRxiv2024

Biological modifications of the immune response to COVID-19 vaccine in patients treated with anti-CD20 agents and immune-checkpoint inhibitors

Investigating the impact of immune-modulating therapies on mRNA vaccine efficacy transcends the immediate context of the COVID-19 pandemic. This study focuses on the differential immune responses to the third dose of COVID-19 mRNA vaccine among healthy volunteers, cancer patients treated with immune-checkpoint inhibitors (ICIs), and those treated with the anti-CD20 antibody rituximab. Utilizing RNA sequencing, serology, and interferon-{gamma} release assessment, we charted the temporal dynamics of the immune response in such cohorts. Our findings indicate that ICIs maintain an immune profile similar to that of healthy individuals, whereas treatment with rituximab is associated with impairment of type I interferon response and the upregulation of transcripts pertaining to regulatory T cells, with a global dysfunction of both humoral and cellular immunity. This research deepens our understanding of the sophisticated interplay within the immune system in health and disease states, potentially informing therapeutic strategies across a spectrum of immunological conditions. Significance statementOur study examines how cancer treatments that modify the immune system affect transcriptional, serological, and cellular responses to a model for repeated antigenic stimulation in humans, represented by the SARS-CoV-2 booster vaccine. Specifically, we investigated patients treated with rituximab (RTX), which impairs antibody production, and immune checkpoint inhibitors (ICI), which can trigger autoimmune disorders. We discovered that RTX-treated patients not only exhibit a reduced antibody response but actually show a diminished interferon-mediated immune response, indicating a broader immune disruption than anticipated. Conversely, ICI-treated patients responded to the vaccine similarly to healthy individuals, suggesting that fears of adverse vaccine reactions in these patients may be unfounded. This research highlights important considerations for the clinical management of cancer patients receiving these treatments.

immunology↗

bioRxiv2021

High temporal resolution transcriptomic profiling delineates distinct patterns of interferon response following Covid-19 mRNA vaccination and SARS-CoV2 infection

Knowledge of the mechanisms underpinning the development of protective immunity conferred by mRNA vaccines is fragmentary. Here we investigated responses to COVID-19 mRNA vaccination via ultra-low-volume sampling and high-temporal-resolution transcriptome profiling (23 subjects across 22 timepoints, and with 117 COVID-19 patients used as comparators). There were marked differences in the timing and amplitude of the responses to the priming and booster doses. Notably, we identified two distinct interferon signatures. The first signature (A28/S1) was robustly induced both post-prime and post-boost and in both cases correlated with the subsequent development of antibody responses. In contrast, the second interferon signature (A28/S2) was robustly induced only post-boost, where it coincided with a transient inflammation peak. In COVID19 patients, a distinct phenotype dominated by A28/S2 was associated with longer duration of intensive care. In summary, high-temporal-resolution transcriptomic permitted the identification of post- vaccination phenotypes that are determinants of the course of COVID-19 disease.

immunology↗