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. 2025 May 10:55:127023.
doi: 10.1016/j.vaccine.2025.127023. Epub 2025 Mar 23.

Effect of lymphocyte miRNA expression on influenza vaccine-induced immunity

Iana H Haralambieva  1 , Tamar Ratishvili  1 , Krista M Goergen  2 , Diane E Grill  2 , Whitney L Simon  1 , Jun Chen  2 , Inna G Ovsyannikova  1 , Gregory A Poland  1 , Richard B Kennedy  3
Affiliations

Effect of lymphocyte miRNA expression on influenza vaccine-induced immunity

Iana H Haralambieva et al. Vaccine. .

Abstract

Alterations of gene expression by miRNAs contribute substantially to genetic regulation and cellular functions. We conducted a comprehensive study in 53 individuals before and after seasonal inactivated influenza vaccine to characterize lymphocyte-specific miRNA expression (in purified B cells, CD4+ T cells, CD8+ T cells, and NK cells) and its effect on influenza vaccine-induced immune outcomes (hemagglutination inhibition antibody titers/HAI, viral neutralizing antibody titers /VNA, and memory B cell ELISPOT). Overall, we observed relatively stable miRNA expression before and after influenza vaccination. Statistical analysis uncovered three baseline miRNAs (miR-150-3p, miR-629-5p, and miR-4443) that were significantly correlated with influenza vaccine-induced immune outcomes in different cell types. Predictive modeling of influenza vaccine-induced HAI/VNA titers identified a set of specific baseline miRNAs in CD4+ T cells as factors predictive of antibody responses. A pathway enrichment analysis on the putative target genes revealed several regulated signaling pathways and functions: TGF-β signaling, PI3K-Akt signaling, p53 signaling, MAPK signaling, TNF signaling, and C-type lectin receptor signaling, as well as cell adhesion and adherens junctions, and antiviral host response. In conclusion, our study offers evidence for the role of epigenetic modification (miRNAs) on influenza vaccine-induced immunity. After validation, identified miRNAs may serve as potential biomarkers of immune response after influenza vaccination.

Keywords: B cells; Immunity; Influenza vaccine; MicroRNA expression; NK cells; T cells.

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Conflict of interest statement

Declaration of competing interest Dr. Poland is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr. Poland provides consultative advice to AiZtech; GlaxoSmithKline; Merck & Co. Inc.; Moderna; Novavax; Sanofi; Syneos Health; and Valneva. Dr. Poland is an adviser to the White House and World Health Organization on COVID-19 vaccines and monkeypox, respectively. Drs. Poland and Ovsyannikova hold patents related to vaccinia and measles peptide vaccines. Drs. Kennedy, Poland, and Ovsyannikova hold a patent related to vaccinia peptide vaccines. Drs. Poland, Kennedy, Ovsyannikova, and Haralambieva hold a patent related to the impact of single nucleotide polymorphisms on measles vaccine immunity. Drs. Poland, Kennedy, and Ovsyannikova have received grant funding from ICW Ventures for preclinical studies on a peptide-based COVID-19 vaccine. Dr. Kennedy has received funding from Merck Research Laboratories to study waning immunity to mumps vaccine. Dr. Kennedy also offers consultative advice on vaccine development to Merck & Co. and Sanofi Pasteur. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies.

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