Abstract
Age-associated immune changes and pre-existing influenza immunity are hypothesized to reduce influenza vaccine effectiveness in older adults, although the contribution of each factor is unknown. Here, we constructed influenza-specific IgG landscapes and determined baseline concentrations of cytokines typically associated with chronic inflammation in older adults (TNF-α, IL-10, IL-6, and IFN-γ) in 30 high and 29 low influenza vaccine responders (HR and LR, respectively). In a background of high H3 antibody titers, vaccine-specific H3, but not H1, antibody titers were boosted in LRs to titers comparable to HRs. Pre-vaccination concentrations of IL-10 were higher in LRs compared with HRs and inversely correlated with titers of pre-existing influenza antibodies. Baseline TNF-α concentrations were positively correlated with fold-increases in antibody titers in HRs. Our findings indicate that baseline inflammatory status is an important determinant for generating post-vaccination hemagglutinin-inhibition antibodies in older adults, and IgG responses can be boosted in the context of high pre-existing immunity.