Patient subtyping analysis of baseline multi-omic data reveals distinct pre-immune states associated with antibody response to seasonal influenza vaccination

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2024-09, Vol.266, p.110333, Article 110333
• Main Authors: Sevim Bayrak, Cigdem, Forst, Christian V., Jones, Drew R., Gresham, David J., Pushalkar, Smruti, Wu, Shaohuan, Vogel, Christine, Mahal, Lara K., Ghedin, Elodie, Ross, Ted, García-Sastre, Adolfo, Zhang, Bin
• Format: Article
• Language: English
• Subjects: Adaptive Immunity - immunology; Adult; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antibody Formation - immunology; Antibody response; Existing immunity; Female; Hemagglutination Inhibition Tests; Humans; Immunity, Innate - immunology; Immunoglobulin A - blood; Immunoglobulin A - immunology; Influenza; Influenza Vaccines - immunology; Influenza, Human - immunology; Influenza, Human - prevention & control; Male; Middle Aged; Molecular subtyping; Multi-omic integration; Multiomics; Proteomics - methods; Seasons; Vaccination; Vaccine; Young Adult
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2024.110333

Understanding the molecular mechanisms underpinning diverse vaccination responses is critical for developing efficient vaccines. Molecular subtyping can offer insights into heterogeneous nature of responses and aid in vaccine design. We analyzed multi-omic data from 62 haemagglutinin seasonal influenza vaccine recipients (2019–2020), including transcriptomics, proteomics, glycomics, and metabolomics data collected pre-vaccination. We performed a subtyping analysis on the integrated data revealing five subtypes with distinct molecular signatures. These subtypes differed in the expression of pre-existing adaptive or innate immunity signatures, which were linked to significant variation in baseline immunoglobulin A (IgA) and hemagglutination inhibition (HAI) titer levels. It is worth noting that these differences persisted through day 28 post-vaccination, indicating the effect of initial immune state on vaccination response. These findings highlight the significance of interpersonal variation in baseline immune status as a crucial factor in determining the effectiveness of seasonal vaccines. Ultimately, incorporating molecular profiling could enable personalized vaccine optimization. •Five baseline molecular subtypes were identified in the integrated baseline (pre-vaccination) multiomics data.•Molecular subtypes show significant variation in pre- and post-vaccination antibody levels including IgA and HAI.•Molecular subtypes present distinct pre-existing adaptive or innate immune response signatures.•Baseline immune status is essential in determining vaccine response and efficacy.