ABSTRACT
Human cases of avian influenza virus (AIV) infections are associated with an age-specific disease burden. As the influenza virus N2 neuraminidase (NA) gene was introduced from avian sources during the 1957 pandemic, we investigate the reactivity of N2 antibodies against A(H9N2) AIVs. Serosurvey of healthy individuals reveal the highest rates of AIV N2 antibodies in individuals aged ≥65 years. Exposure to the 1968 pandemic N2, but not recent N2, protected against A(H9N2) AIV challenge in female mice. In some older adults, infection with contemporary A(H3N2) virus could recall cross-reactive AIV NA antibodies, showing discernable human- or avian-NA type reactivity. Individuals born before 1957 have higher anti-AIV N2 titers compared to those born between 1957 and 1968. The anti-AIV N2 antibodies titers correlate with antibody titers to the 1957 N2, suggesting that exposure to the A(H2N2) virus contribute to this reactivity. These findings underscore the critical role of neuraminidase immunity in zoonotic and pandemic influenza risk assessment.
Subject(s)
Antibodies, Viral , Cross Reactions , Influenza A Virus, H3N2 Subtype , Influenza, Human , Neuraminidase , Pandemics , Neuraminidase/immunology , Neuraminidase/genetics , Animals , Humans , Antibodies, Viral/immunology , Antibodies, Viral/blood , Influenza A Virus, H3N2 Subtype/immunology , Female , Cross Reactions/immunology , Mice , Influenza, Human/immunology , Influenza, Human/epidemiology , Influenza, Human/virology , Aged , Influenza A Virus, H2N2 Subtype/immunology , Influenza A Virus, H2N2 Subtype/genetics , Male , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/virology , Orthomyxoviridae Infections/epidemiology , Orthomyxoviridae Infections/veterinary , Birds/virology , Middle Aged , Influenza in Birds/epidemiology , Influenza in Birds/immunology , Influenza in Birds/virology , Influenza A Virus, H9N2 Subtype/immunology , Adult , Viral Proteins/immunology , Viral Proteins/geneticsABSTRACT
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.