Broader antibody responses in females than males following seasonal influenza vaccination: a biophysical and functional analysis 4338

Description quadrivalent influenza vaccine (QIV) among HCWs aged 18–45. Using plasma collected at baseline and 28-days post-vaccination (DPV), we assessed antibody activities against influenza A/B viruses using systems serology. Live virus-neutralizing antibody (nAb) levels against H1N1 and H3N2 vaccine strains were measured to evaluate antiviral responses. nAb titers increased in both males and females post-vaccination, with 63% of males and 66% of females seroconverting (nAb fold-change > 4). Among seroconverters, females had significantly higher H3N2 nAb responses than males, while H1N1 responses were similar. Baseline and 28 DPV samples from seroconverters were further analyzed using multiplexed assays to assess antigen-specific immunoglobulin isotype responses and Fc receptor binding affinity. Females showed stronger IgA responses to both H1 and H3, reflected by higher FcαRI binding, indicating stronger IgA affinity. Additionally, females mounted higher total IgG and IgG3 responses to H3, which correlated with increased FcγRIIIA binding, known for strong IgG3 affinity. These findings highlight sex-based differences in vaccine-induced antibody responses, with analyses of non-neutralizing functional responses ongoing. Funding Sources Funding provided the National Institutes of Health NIA/ORWH Johns Hopkins Specialized Center of Research Excellence (U54AG062333; SLK) and the NIAID Johns Hopkins Center of Excellence for Influenza Research and Response (75N93021C00045; AP and RR).