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IL-8 as a potential link between aging and impaired influenza antibody responses in older adults

Quach, H. Q.; Goergen, K. M.; Grill, D. E.; Ovsyannikova, I. G.; Poland, G. A.; Kennedy, R. B.

2024-11-08 allergy and immunology
10.1101/2024.11.07.24316936 medRxiv
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BackgroundAntibody responses to MF59-adjuvanted (MF59Flu) and high-dose (HDFlu) influenza vaccines have been well-characterized in older adults, yet corresponding cellular response data remain limited. MethodsBlood samples were collected from 106 MF59Flu recipients and 112 HDFlu recipients before vaccination (Day 0), and on Days 1, 8, and 28 post-vaccination. Antibody responses were assessed on Days 0, 8, and 28 using a hemagglutination inhibition (HAI) assay. Eight pro-inflammatory cytokines and chemokines, including IFN-2a, IFN-{gamma}, IP-10, MCP-1, MIP-1, IL-1{beta}, IL-6, IL-8, were quantified from PBMCs collected on Days 0 and 1 following stimulation with live influenza A/H3N2 virus using a multiplex assay. Associations between cytokine/chemokine levels and HAI titers were examined, along with the effect of sex, age, body mass index (BMI), and cytomegalovirus infection status. ResultsVaccine type (MF59Flu or HDFlu), sex, BMI and cytomegalovirus infection did not significantly impact cytokine and chemokine levels. However, age was positively correlated with IL-8 level on Day 1 (r = 0.24, p = 0.0003) as well as the change in IL-8 levels from Day 1 to Day 0 (r = 0.16, p = 0.021). Notably, the change in IL-8 levels was negatively associated with peak antibody responses at Day 28 (r = -0.15, p = 0.026). ConclusionOur findings underscore IL-8 as a potential link between aging and impaired antibody responses to influenza vaccination in older adults, suggesting that IL-8 inhibition could be a promising molecular intervention to improve immunogenicity and efficacy of influenza vaccines in this high-risk population.

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