Ratishvili, Tamar

Abstract Background While 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. Methods We 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. Results CMV 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) Conclusions Our 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.

AbstractBackgroundA third dose of measles-mumps-rubella vaccine (MMR3) is recommended in mumps outbreak scenarios, but the immune response and the need for widespread use of MMR3 remain uncertain. Herein, we characterized measles-specific immune responses to MMR3 in a cohort of 232 healthy subjects.MethodsSerum and peripheral blood mononuclear cells (PBMCs) were sampled at day 0 and day 28 after MMR3. Measles-specific binding and neutralizing antibodies were quantified in sera by enzyme-linked immunosorbent assay and a microneutralization assay, respectively. PBMCs were stimulated with inactivated measles virus, and the release of cytokines/chemokines was assessed by a multiplex assay. Demographic variables of subjects were examined for potential correlations with immune outcomes.ResultsOf the study participants, 95.69% and 100% were seropositive at day 0 and day 28, respectively. Antibody avidity significantly increased from 38.08% at day 0 to 42.8% at day 28 (P = .00026). Neutralizing antibodies were significantly enhanced, from 928.7 at day 0 to 1289.64 mIU/mL at day 28 (P = .0001). Meanwhile, cytokine/chemokine responses remained largely unchanged. Body mass index was significantly correlated with the levels of inflammatory cytokines/chemokines.ConclusionsMeasles-specific humoral immune responses, but not cellular responses, were enhanced after MMR3 receipt, extending current understanding of immune responses to MMR3 and supporting MMR3 administration to seronegative or high-risk individuals.