title: The impact of immunosenescence on humoral immune response variation after influenza A/H1N1 vaccination in older subjects.
abstract: BACKGROUND
  Although influenza causes significant morbidity and mortality in the elderly, the factors underlying the reduced vaccine immunogenicity and efficacy in this age group are not completely understood. Age and immunosenescence factors, and their impact on humoral immunity after influenza vaccination, are of growing interest for the development of better vaccines for the elderly.
  
  
  METHODS
  We assessed associations between age and immunosenescence markers (T cell receptor rearrangement excision circles - TREC content, peripheral white blood cell telomerase - TERT expression and CD28 expression on T cells) and influenza A/H1N1 vaccine-induced measures of humoral immunity in 106 older subjects at baseline and three timepoints post-vaccination.
  
  
  RESULTS
  TERT activity (TERT mRNA expression) was significantly positively correlated with the observed increase in the influenza-specific memory B cell ELISPOT response at Day 28 compared to baseline (p-value=0.025). TREC levels were positively correlated with the baseline and early (Day 3) influenza A/H1N1-specific memory B cell ELISPOT response (p-value=0.042 and p-value=0.035, respectively). The expression and/or expression change of CD28 on CD4+ and/or CD8+ T cells at baseline and Day 3 was positively correlated with the influenza A/H1N1-specific memory B cell ELISPOT response at baseline, Day 28 and Day 75 post-vaccination. In a multivariable analysis, the peak antibody response (HAI and/or VNA at Day 28) was negatively associated with age, the percentage of CD8+CD28 low T cells, IgD+CD27- naïve B cells, and percentage overall CD20- B cells and plasmablasts, measured at Day 3 post-vaccination. The early change in influenza-specific memory B cell ELISPOT response was positively correlated with the observed increase in influenza A/H1N1-specific HAI antibodies at Day 28 and Day 75 relative to baseline (p-value=0.007 and p-value=0.005, respectively).
  
  
  CONCLUSIONS
  Our data suggest that influenza-specific humoral immunity is significantly influenced by age, and that specific markers of immunosenescence (e.g., the baseline/early expression of CD28 on CD4+ and/or CD8+ T cells and T cell immune abnormalities) are correlated with different humoral immune response outcomes observed after vaccination in older individuals, and thus can be potentially used to predict vaccine immunogenicity.
authors: Mayo Vaccine Research Group, Mayo Clinic, Rochester, Minnesota, United States of America; Program in Translational Immunovirology and Biodefense, Mayo Clinic, Rochester, Minnesota, United States of America.
authors: Iana H
authors: IH
authors: Haralambieva
authors: Mayo Vaccine Research Group, Mayo Clinic, Rochester, Minnesota, United States of America.
authors: Scott D
authors: SD
authors: Painter
authors: Mayo Vaccine Research Group, Mayo Clinic, Rochester, Minnesota, United States of America; Program in Translational Immunovirology and Biodefense, Mayo Clinic, Rochester, Minnesota, United States of America.
authors: Richard B
authors: RB
authors: Kennedy
authors: Mayo Vaccine Research Group, Mayo Clinic, Rochester, Minnesota, United States of America; Program in Translational Immunovirology and Biodefense, Mayo Clinic, Rochester, Minnesota, United States of America.
authors: Inna G
authors: IG
authors: Ovsyannikova
authors: Mayo Vaccine Research Group, Mayo Clinic, Rochester, Minnesota, United States of America; Program in Translational Immunovirology and Biodefense, Mayo Clinic, Rochester, Minnesota, United States of America.
authors: Nathaniel D
authors: ND
authors: Lambert
authors: Mayo Vaccine Research Group, Mayo Clinic, Rochester, Minnesota, United States of America; Division of Biomedical Statistics and Informatics - Department of Health Science Research, Mayo Clinic, Rochester, Minnesota, United States of America.
authors: Krista M
authors: KM
authors: Goergen
authors: Mayo Vaccine Research Group, Mayo Clinic, Rochester, Minnesota, United States of America; Division of Biomedical Statistics and Informatics - Department of Health Science Research, Mayo Clinic, Rochester, Minnesota, United States of America.
authors: Ann L
authors: AL
authors: Oberg
authors: Mayo Vaccine Research Group, Mayo Clinic, Rochester, Minnesota, United States of America; Program in Translational Immunovirology and Biodefense, Mayo Clinic, Rochester, Minnesota, United States of America; Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, United States of America.
authors: Gregory A
authors: GA
authors: Poland
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D056724:Immunity, Humoral; D000068884:Immunosenescence; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology; D007251:Influenza, Human / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019098:Telomerase / Q000235:genetics; D013997:Time Factors; D014611:Vaccination
chemical_list: D007252:Influenza Vaccines; D019098:Telomerase