Similar humoral responses but distinct CD4+ T cell transcriptomic profiles in older adults elicited by MF59 adjuvanted and high dose influenza vaccines

Sci Rep. 2024 Oct 18;14(1):24420. doi: 10.1038/s41598-024-75250-2.

Abstract

Older age (≥ 65 years) is associated with impaired responses to influenza vaccination, leading to the preferential recommendation of MF59-adjuvanted (MF59Flu) or high-dose (HDFlu) influenza vaccines for this age group in the United States. Herein, we characterized transcriptomic profiles of CD4+ T cells isolated from 234 recipients (≥ 65 years) of either MF59Flu or HDFlu vaccine, prior to vaccination and 28 days thereafter. We identified 412 and 645 differentially expressed genes (DEGs) in CD4+ T cells of older adults after receiving MF59Flu and HDFlu, respectively. DEGs in CD4+ T cells of MF59Flu recipients were enriched in 14 KEGG pathways, all of which were downregulated. DEGs in CD4+ T cells of HDFlu recipients were enriched in 11 upregulated pathways and 20 downregulated pathways. CD4+ T cells in both vaccine groups shared 50 upregulated genes and 75 downregulated genes, all of which were enriched in 7 KEGG pathways. The remaining 287 and 520 DEGs were specifically associated with MF59Flu and HDFlu, respectively. Unexpectedly, none of these DEGs was significantly correlated with influenza A/H3N2-specific HAI titers, suggesting these DEGs at the individual level may have a limited role in protection against influenza. Our findings emphasize the need for further investigation into other factors influencing immunity against influenza in older adults.

Keywords: CD4+ T cells; Gene expression profiling; High-dose influenza vaccine; MF59-adjuvanted influenza vaccine; Older adults.

MeSH terms

  • Adjuvants, Immunologic*
  • Aged
  • Aged, 80 and over
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • CD4-Positive T-Lymphocytes* / immunology
  • CD4-Positive T-Lymphocytes* / metabolism
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunity, Humoral / immunology
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza Vaccines* / immunology
  • Influenza, Human* / immunology
  • Influenza, Human* / prevention & control
  • Male
  • Polysorbates* / pharmacology
  • Squalene* / pharmacology
  • Transcriptome*
  • Vaccination

Substances

  • Influenza Vaccines
  • MF59 oil emulsion
  • Squalene
  • Polysorbates
  • Adjuvants, Immunologic
  • Antibodies, Viral