Cytomegalovirus serostatus and plasma MCP-1 levels are associated with antibody response to seasonal influenza vaccine across age and sex

BackgroundWhile immunologic aging impacts immune responses to vaccination, consistent biomarkers associated with aging of the immune system and suboptimal serologic response to influenza vaccination have not been well-studied. Identification of readily measurable biomarkers of immunosenescence may have predictive clinical utility and inform targeted influenza vaccination strategies and future research into aging of the immune system. MethodsWe quantified multiple serum/plasma and cell-based parameters related to immune aging (CMV serostatus, plasma cytokines/chemokines, TREC, TERT, NK cell functionality, and DNA methylation clock) at baseline in an adult (age range 18-85) cohort of 2019-2020 influenza vaccine recipients (n=337) and evaluated their associations with vaccine-induced HAI response to influenza A/H1N1, A/H3N2 and B/Victoria strains. ResultsCMV IgG titers were significantly positively correlated with vaccine-induced increases in HAI antibody titers to influenza A/H1N1 (p=0.02) and A/H3N2 (p=0.014). CMV IgG titers (p=0.00096) and CMV seropositivity (p=0.003) were also associated with Day 28 HAI seropositivity against influenza A/H3N2 in subjects seronegative at baseline. Conversely, plasma MCP-1 levels were negatively associated with HAI responses to the A/H3N2 (p=0.04) strain. These findings were significant independent of age, sex or vaccine type received (high vs standard-dose seasonal influenza vaccine) ConclusionsOur identification of significant relationships between easily quantifiable immune markers and HAI responses to influenza A vaccine strains across sex and age enhances our knowledge of specific links between immune aging and influenza vaccine-induced immunity. These markers could be leveraged for predicting response to influenza immunization.