The impact of physical frailty on the response to inactivated influenza vaccine in older adults

Abstract

Physical frailty's impact on hemagglutination inhibition antibody titers (HAI) and peripheral blood mononuclear cell (PBMC) transcriptional responses after influenza vaccination is unclear. Physical frailty was assessed using the 5-item Fried frailty phenotype in 168 community- and assisted-living adults ≥55 years of age during an observational study. Blood was drawn before, 3, 7, and 28 days post-vaccination with the 2017-2018 inactivated influenza vaccine. HAI response to the A/H1N1 strain was measured at Days 0 and 28 using seropositivity, seroconversion, log₂ HAI titers, and fold-rise in log₂ HAI titers. RNA sequencing of PBMCs from Days 0, 3 and 7 was measured in 28 participants and compared using pathway analyses. Frailty was not significantly associated with any HAI outcome in multivariable models. Compared with non-frail participants, frail participants expressed decreased cell proliferation, metabolism, antibody production, and interferon signaling genes. Conversely, frail participants showed elevated gene expression in IL-8 signaling, T-cell exhaustion, and oxidative stress pathways compared with non-frail participants. These results suggest that reduced effectiveness of influenza vaccine among older, frail individuals may be attributed to immunosenescence-related changes in PBMCs that are not reflected in antibody levels.

Keywords: antibody titers; frailty; immune response; influenza; peripheral cell mediated immunity.

Figure 1

Heat maps comparing frail to non-frail on day 0 (A), day 3 (B), and day 7 (C) post-vaccination. Lower expression of genes involved in cellular movement, hematological development and function, immune cell trafficking, and inflammatory response can be observed in the frail group compared with non-frail on day 0 and day 3. Higher expression of genes involved cellular movement, cell-to-cell signaling and interaction, and cellular development is shown in the frail group compared with non-frail on day 7. Genes involved in infectious diseases were consistently expressed at higher levels in frail versus non-frail adults at all three time points.