Research Paper Volume 7, Issue 1 pp 38—51
Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination
- 1 Department of Pathology, Yale School of Medicine, New Haven CT 06520, USA
- 2 Interdepartmental Program in Computational Biology and Bioinformatics, Yale School of Medicine, New Haven, CT 06520, USA
- 3 Section of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA
- 4 Department of Pathology and Genetics, Yale School of Medicine, New Haven CT 06520, USA
- 5 Center for Vaccine Development, Saint Louis University, St. Louis, MO 63104, USA
- 6 Department of Internal Medicine, Yale School of Medicine, New Haven, CT 0652, USA
- 7 Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA
- 8 Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, USA
- 9 Department of Biostatistics and Computational Biology, University of Rochester, Rochester NY 14642, USA
Received: November 25, 2014 Accepted: January 12, 2015 Published: January 14, 2015https://doi.org/10.18632/aging.100720
How to Cite
Copyright: © 2015 Thakar et al.
To elucidate gene expression pathways underlying age-associated impairment in influenza vaccine response, we screened young (age 21-30) and older (age ≥65) adults receiving influenza vaccine in two consecutive seasons and identified those with strong or absent response to vaccine, including a subset of older adults meeting criteria for frailty. PBMCs obtained prior to vaccination (Day 0) and at day 2 or 4, day 7 and day 28 post-vaccine were subjected to gene expression microarray analysis. We defined a response signature and also detected induction of a type I interferon response at day 2 and a plasma cell signature at day 7 post-vaccine in young responders. The response signature was dysregulated in older adults, with the plasma cell signature induced at day 2, and was never induced in frail subjects (who were all non-responders). We also identified a mitochondrial signature in young vaccine responders containing genes mediating mitochondrial biogenesis and oxidative phosphorylation that was consistent in two different vaccine seasons and verified by analyses of mitochondrial content and protein expression. These results represent the first genome-wide transcriptional profiling analysis of age-associated dynamics following influenza vaccination, and implicate changes in mitochondrial biogenesis and function as a critical factor in human vaccine responsiveness.