Systemic dysregulation and molecular insights into poor influenza vaccine response in the aging population
Vaccination-induced protection against influenza is greatly diminished and increasingly heterogeneous with age. We investigated longitudinally (up to five time points) a cohort of 234 vaccinated >65-year-old vaccinees with adjuvanted vaccine FluAd across two independent seasons. System-level analyses of multiomics datasets measuring six modalities and serological data revealed that poor responders lacked time-dependent changes in response to vaccination as observed in responders, suggestive of systemic dysregulation in poor responders. Multiomics integration revealed key molecules and their likely role in vaccination response. High prevaccination plasma interleukin-15 (IL-15) concentrations negatively associated with antibody production, further supported by experimental validation in mice revealing an IL-15-driven natural killer cell axis explaining the suppressive role in vaccine-induced antibody production as observed in poor responders. We propose a subset of long-chain fatty acids as modulators of persistent inflammation in poor responders. Our findings provide a potential link between low-grade chronic inflammation and poor vaccination response and open avenues for possible pharmacological interventions to enhance vaccine responses.
Authors
- Nhan Nguyen (ORCID: https://orcid.org/0000-0001-8720-1195)
- Martijn Zoodsma (ORCID: https://orcid.org/0000-0003-3636-2209)
- Ahmed Alaswad (ORCID: https://orcid.org/0000-0003-1770-1332)
- Saumya Kumar (ORCID: https://orcid.org/0000-0001-9481-1944)
- Stephanie Trittel (ORCID: https://orcid.org/0000-0002-9719-9161)
- Carlos A. Guzmán (ORCID: https://orcid.org/0000-0002-2913-5254)
- Haroon Arshad (ORCID: https://orcid.org/0000-0002-3488-0064)
- Rodrigo Pedroso (ORCID: https://orcid.org/0000-0001-6266-8100)
- Cheng‐Jian Xu (ORCID: https://orcid.org/0000-0003-1586-4672)
- Frank Peßler (ORCID: https://orcid.org/0000-0002-3434-2311)
- Peggy Riese (ORCID: https://orcid.org/0000-0001-6796-6780)
- Luís Graça (ORCID: https://orcid.org/0000-0001-6935-8500)
- Javier Botey-Bataller (ORCID: https://orcid.org/0000-0003-3512-3150)
- Yang Li (ORCID: https://orcid.org/0000-0003-4022-7341)
- Liang Zhou (ORCID: https://orcid.org/0000-0002-0462-4131)
- Mihai G. Netea (ORCID: https://orcid.org/0000-0003-2421-6052)
Institutions
- University of Bonn (DE)
- University of Lisbon (PT)
- Radboud University Nijmegen (NL)
- Radboud University Medical Center (NL)
- Medizinische Hochschule Hannover (DE)
- Helmholtz Centre for Infection Research (DE)
- Centre for Individualised Infection Medicine (DE)
- Center for Experimental and Clinical Infection Research (DE)
- Artificial Intelligence in Medicine (Canada) (CA)
Publication Details
- Journal
- Science Advances
- Published
- 2024-09-27
- DOI
- https://doi.org/10.1126/sciadv.adq7006
- Citations
- 10
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 2.40
Funders
- Medizinischen Hochschule Hannover