Immune response to influenza vaccination in the elderly is altered by chronic medication use

Abstract

BackgroundThe elderly patient population is the most susceptible to influenza virus infection and its associated complications. Polypharmacy is common in the aged, who often have multiple co-morbidities. Previous studies have demonstrated that commonly used prescription drugs can have extensive impact on immune defenses and responses to vaccination. In this study, we examined how the dynamics of immune responses to the two influenza A virus strains of the trivalent inactivated influenza vaccine (TIV) can be affected by patient’s history of using the prescription drugs Metformin, NSAIDs or Statins.ResultsWe provide evidence for differential antibody (Ab) production, B-cell phenotypic changes, alteration in immune cell proportions and transcriptome-wide perturbation in individuals with a history of long-term medication use, compared with non-users. We noted a diminished response to TIV in the elderly on Metformin, whereas those on NSAIDs or Statins had higher baseline responses but reduced relative increases in virus-neutralizing Abs (VNAs) or Abs detected by an enzyme-linked immunosorbent assay (ELISA) following vaccination.ConclusionCollectively, our findings suggest novel pathways that might underlie how long-term medication use impacts immune response to influenza vaccination in the elderly. They provide a strong rationale for targeting the medication-immunity interaction in the aged population to improve vaccination responses.Electronic supplementary materialThe online version of this article (10.1186/s12979-018-0124-9) contains supplementary material, which is available to authorized users.

Age-related changes in B cell metabolism

“…The effect of aging on one-carbon metabolism has not yet been studied in detail but our data show that this pathway may not only decline in the aged but also respond less vigorously to increasing demands imposed by cell stimulation. Metformin, a commonly-used anti-diabetes drug impairs one-carbon metabolism [52] and as we reported reduces antibody responses to TIV in aged individuals again providing supporting evidence for the essential role of one-carbon metabolism on B cell functions [53].…”

Vaccine-induced ICOS+CD38+ circulating Tfh are sensitive biosensors of age-related changes in inflammatory pathways

“…These signatures were then used to test whole-blood microarray data from other years’ cohorts from the same study. 64 , 65 We found strong enrichment of the signatures of youth and aging in the young and elderly adults, respectively ( Figure 6 A). The signature of youth had Gene Ontology terms for RNA metabolism, whereas the signature of aging had terms for fatty acid metabolism and cytoskeletal regulation ( Figure S6 B), in agreement with other signatures of aging.…”

Vaccine-induced ICOS+CD38+ cTfh are sensitive biosensors of age-related changes in inflammatory pathways

“…From these data, we constructed signatures of youth (354 genes upregulated in the young) or aging (232 genes upregulated in the elderly) (Supplemental Table 6 -7, Supplemental Figure 6A). These signatures were then used to test whole-blood microarray data from other years' cohorts from the same study (48,49). We found strong enrichment of the signatures of youth and aging in the young and elderly adults, respectively (Figure 6A).…”