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J Infect Dis
. 2025 Mar 17:jiaf148.
doi: 10.1093/infdis/jiaf148. Online ahead of print. IL-8 as a Causal Link Between Aging and Impaired Influenza Antibody Responses in Older Adults
Huy Quang Quach 1 , Krista M Goergen 2 , Diane E Grill 2 , Inna G Ovsyannikova 1 , Gregory A Poland 1 3 , Richard B Kennedy 1
Affiliations
Background: Antibody responses to MF59-adjuvanted (MF59Flu) and high-dose (HDFlu) influenza vaccines have been well-characterized in older adults, yet corresponding cellular immune response data remain limited.
Methods: Blood samples were collected from 106 MF59Flu recipients and 112 HDFlu recipients at four time points: before vaccination (Day 0), and on Days 1, 8, and 28 post-vaccination. Antibody responses were assessed in serum samples using a hemagglutination inhibition assay. Eight pro-inflammatory cytokines and chemokines, including IFN-α2a, IFN-γ, IP-10, MCP-1, MIP-1α, IL-1β, IL-6, and IL-8, were quantified from PBMCs using a multiplex assay. Associations between cytokine/chemokine secretion levels and antibody responses were examined, along with the effect of sex, age, body mass index (BMI), and cytomegalovirus infection status.
Results: Age was positively correlated with IL-8 levels on Day 1 (r = 0.24, p < 0.001) and the change in IL-8 levels from Day 0 to Day 1 (r = 0.16, p = 0.021). Notably, the change in IL-8 levels was negatively associated with Day 28 HAI titers (r = -0.15, p = 0.026). Causal mediation analysis demonstrated that IL-8 exerted significant causal mediation effects on antibody responses at both Day 8 (p = 0.046) and Day 28 (p = 0.0045). No significant effects of other cytokines and chemokines, vaccine type, sex, or BMI on antibody responses were observed.
Conclusion: Our findings underscore IL-8 as a potential mediator of antibody responses to influenza vaccination in older adults, suggesting that IL-8 inhibition could serve as a molecular intervention to improve antibody responses in this high-risk population.
Keywords: HDFlu; Influenza vaccine; MF59Flu; antibody; chemokines; cytokines; older adults.
. 2025 Mar 17:jiaf148.
doi: 10.1093/infdis/jiaf148. Online ahead of print. IL-8 as a Causal Link Between Aging and Impaired Influenza Antibody Responses in Older Adults
Huy Quang Quach 1 , Krista M Goergen 2 , Diane E Grill 2 , Inna G Ovsyannikova 1 , Gregory A Poland 1 3 , Richard B Kennedy 1
Affiliations
- PMID: 40091229
- DOI: 10.1093/infdis/jiaf148
Background: Antibody responses to MF59-adjuvanted (MF59Flu) and high-dose (HDFlu) influenza vaccines have been well-characterized in older adults, yet corresponding cellular immune response data remain limited.
Methods: Blood samples were collected from 106 MF59Flu recipients and 112 HDFlu recipients at four time points: before vaccination (Day 0), and on Days 1, 8, and 28 post-vaccination. Antibody responses were assessed in serum samples using a hemagglutination inhibition assay. Eight pro-inflammatory cytokines and chemokines, including IFN-α2a, IFN-γ, IP-10, MCP-1, MIP-1α, IL-1β, IL-6, and IL-8, were quantified from PBMCs using a multiplex assay. Associations between cytokine/chemokine secretion levels and antibody responses were examined, along with the effect of sex, age, body mass index (BMI), and cytomegalovirus infection status.
Results: Age was positively correlated with IL-8 levels on Day 1 (r = 0.24, p < 0.001) and the change in IL-8 levels from Day 0 to Day 1 (r = 0.16, p = 0.021). Notably, the change in IL-8 levels was negatively associated with Day 28 HAI titers (r = -0.15, p = 0.026). Causal mediation analysis demonstrated that IL-8 exerted significant causal mediation effects on antibody responses at both Day 8 (p = 0.046) and Day 28 (p = 0.0045). No significant effects of other cytokines and chemokines, vaccine type, sex, or BMI on antibody responses were observed.
Conclusion: Our findings underscore IL-8 as a potential mediator of antibody responses to influenza vaccination in older adults, suggesting that IL-8 inhibition could serve as a molecular intervention to improve antibody responses in this high-risk population.
Keywords: HDFlu; Influenza vaccine; MF59Flu; antibody; chemokines; cytokines; older adults.