BNT162b2 mRNA vaccination affects the gut microbiome composition of patients with follicular lymphoma and chronic lymphocytic leukemia.

Publication date: Feb 10, 2025

In both chronic lymphatic leukemia (CLL) and follicular lymphoma (FL) immunotherapy determines B-depletion that leads to temporary suppression of humoral immunity, which is clinically relevant especially during the COVID-19 pandemic, when most patients in the first wave received the BNT162b2 vaccine during anti-neoplastic treatment. To capture changes in the immunome and microbiome composition in CLL and FL patients upon mRNA-based vaccination, we designed a prospective, longitudinal study to profile both the humoral and the cellular response after exposure to the BNT162b2 COVID-19 vaccine. In both CLL patients and FL patients, the second and third administrations of the BNT162b2 vaccine increased the titer of specific antibodies against SARS-CoV-2. In FL patients, vaccination induced expansion of central memory CD8 + CD57dim CD279 + T cells and reduction of the neutrophil subset myeloid 1 (CD14CD15CD16CD64CD33CD38PDL1HLA-DR); in both cohorts, CD45RA + CD27 + CD279 + NK cells were expanded after a full cycle of vaccination. After vaccination, the genera Collinsella, Gemmiger, Lachnospiraceae, Blautia, Ruminococcus and Lactobacillus increased in both CLL patients and FL patients, whereas Faecalibacterium, Enterobacteriacae, and Enterococcus decreased. Multivariate analysis failed to identify factors associated with changes in microbiome communities among the CLL and FL cohorts, considering age, sex, exposure to anti-CD20 therapy and disease activity. Only in FL patients, alpha diversity was negatively correlated with neutrophil subsets myeloid 1 e 5 at baseline and positively correlated with neutrophil subset 6 after vaccination. PICRUSt2 analysis showed how microbiome can also affect the host health promoting chronic inflammation. The L-lysine biosynthesis pathway was more represented in CLL patients, whereas the L-valine degradation pathway and the anaerobic degradation of purine nucleobases were overrepresented in the FL cohort. Taken together, our findings reveal the effect of the BNT162b2 vaccine in shaping the microbiome composition in CLL and FL patients, despite receiving treatment for their underlying active disease, and highlight the importance of a comprehensive analysis of the immunome and microbiome profiling to understand immune function in these cohorts of patients.

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Concepts Keywords
Cd57dim Chronic lymphatic leukemia
Host COVID-19
Immunotherapy Follicular lymphoma
Leukemia Immunome
Microbiome profiling
Myeloid composition
Vaccination

Semantics

Type Source Name
disease MESH follicular lymphoma
disease MESH chronic lymphocytic leukemia
disease MESH COVID-19 pandemic
disease IDO host
disease MESH inflammation
disease MESH lymphoma
disease MESH lymphocytic leukemia
pathway REACTOME Reproduction
disease MESH malignancies
disease MESH abnormalities
disease IDO cell
disease MESH death
pathway REACTOME Immune System
drug DRUGBANK Indoleacetic acid
drug DRUGBANK Rituximab
drug DRUGBANK Obinutuzumab
disease MESH lymphoproliferative disorders
drug DRUGBANK Coenzyme M
disease MESH co infection
drug DRUGBANK Sulfamethoxazole
drug DRUGBANK Trimethoprim
drug DRUGBANK Acyclovir
disease IDO blood
drug DRUGBANK Heparin
pathway REACTOME Metabolism
disease IDO assay
disease IDO protein
drug DRUGBANK Edetic Acid
drug DRUGBANK Mitomycin
drug DRUGBANK Trestolone
disease IDO algorithm
disease IDO process
disease MESH infections
disease IDO infection
disease IDO production
drug DRUGBANK Flunarizine
drug DRUGBANK Proline
drug DRUGBANK Hyaluronic acid
disease IDO bacteria
drug DRUGBANK Hexachlorophene
drug DRUGBANK Inositol
drug DRUGBANK Formaldehyde
drug DRUGBANK 3-phenylpropionic acid
drug DRUGBANK L-Phenylalanine
drug DRUGBANK Pentaerythritol tetranitrate
drug DRUGBANK Formic Acid
drug DRUGBANK Ethanol
pathway KEGG Metabolic pathways
drug DRUGBANK Ibrutinib
disease MESH seroconversion
disease IDO immune response
drug DRUGBANK Butyric Acid
drug DRUGBANK Acetate ion
disease MESH dysbiosis
pathway REACTOME Fatty acids
drug DRUGBANK Alpha-Linolenic Acid
pathway REACTOME Apoptosis
disease IDO pathogen
drug DRUGBANK Ursodeoxycholic acid
disease MESH cytokine storm syndrome
disease IDO commensal
disease MESH bacteremia
disease MESH obesity
drug DRUGBANK L-Lysine
pathway REACTOME Acetylation
drug DRUGBANK Amino acids
drug DRUGBANK L-Valine
drug DRUGBANK Coenzyme A
disease MESH metabolic diseases
drug DRUGBANK Uric Acid
drug DRUGBANK Diethylpropion
disease MESH Leukemia
disease MESH hematological malignancies
disease MESH Bulla
disease MESH multiple myeloma
drug DRUGBANK Ruxolitinib
disease MESH myelofibrosis
disease MESH polycythemia vera
disease MESH breakthrough infection
disease MESH Cognitive Impairments
disease IDO quality
drug DRUGBANK (S)-Des-Me-Ampa
disease MESH non Hodgkin lymphoma
drug DRUGBANK Guanosine
pathway KEGG Tight junction
disease MESH necrotizing enterocolitis
disease MESH inflammatory bowel diseases
disease MESH ulcerative colitis
disease IDO opportunistic pathogen
disease MESH Crohn’s disease
disease MESH lung cancer
disease MESH insulin resistance
pathway KEGG Insulin resistance

Original Article

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