ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1662942
Elevated NK and T cell associated cytokines in plasma associate with serological response to influenza vaccination
Provisionally accepted
- 1University of California, Los Angeles, Los Angeles, United States
- 2University of Georgia College of Veterinary Medicine, Athens, United States
- 3Cleveland Clinic Florida Research and Innovation Center, Port St. Lucie, United States
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Numerous pre-vaccination factors are known to be associated with differential responses to influenza vaccination, including age, prior infection, vaccination history, immune cell frequencies, and transcriptomic profiles. However, plasma chemokines and cytokines are relatively unexplored. Given that older individuals have generally higher levels of inflammatory molecules in circulation, termed inflammaging, and also respond poorly to vaccination, plasma immune profiles likely play a role in effective response to influenza vaccination.A cohort of 100 people were sampled pre-(Day-0) and post-vaccination (Day-7) with the inactivated, quadrivalent FluZone construct in the autumn of 2019 (UGA4). Plasma chemokines and cytokines were quantified by 38-plex Luminex assay, with ultra-sensitive quantification of additional analytes by Simoa assay. Antibodies against individual strains of influenza and serological response to vaccination were determined by Day-0 hemagglutination inhibition (HAI) titer and change in HAI titers from Day-0 to Day-28 respectively.Age was strongly associated with pre-vaccination HAI titers and differences in plasma analytes, but not change in HAI titers post-vaccination. High plasma levels of Eotaxin (CCL11) and MDC (CCL22) pre-vaccination were associated respectively with ineffective and effective serological response to vaccination. Increasing plasma levels of IFN-γ, IL-17A, and IL-15 from Day-0 to Day-7 post-vaccination were associated with effective serological response to vaccination.In conclusion, plasma chemokines and cytokines levels prior to or in the first few days postinfluenza vaccination may be predictive of serological responses to vaccination, with changes in IFN-γ, IL-17A, and IL-15 post-vaccination possibly indicative of activation of cell-mediated immunity. These findings support the need for larger, high-resolution studies exploring the role of plasma proteomics in serological responses to influenza vaccination.
Keywords: influenza, FluZone vaccination, Chemokines, Cytokines, serological immunity
Received: 09 Jul 2025; Accepted: 18 Jul 2025.
Copyright: © 2025 Pickering, Carlock, Cappelletti, Gjertson, Ross and Reed. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Elaine F Reed, University of California, Los Angeles, Los Angeles, United States
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