Markers of systemic inflammation are positively associated with influenza vaccine antibody responses with a possible role for ILT2(+)CD57(+) NK-cells

Emilie Picard, Sarah Armstrong, Melissa K. Andrew, Laura Haynes, Mark Loeb, Graham Pawelec, George A. Kuchel, Janet E. McElhaney, Chris P. Verschoor

Résultat de recherche: Articleexamen par les pairs

9 Citations (Scopus)

Résumé

Background: With increasing age, overall health declines while systemic levels of inflammatory mediators tend to increase. Although the underlying mechanisms are poorly understood, there is a wealth of data suggesting that this so-called “inflammaging” contributes to the risk of adverse outcomes in older adults. We sought to determine whether markers of systemic inflammation were associated with antibody responses to the seasonal influenza vaccine. Results: Over four seasons, hemagglutination inhibition antibody titres and ex vivo bulk peripheral blood mononuclear cell (PBMC) responses to live influenza viruses assessed via interferon (IFN)-γ/interleukin (IL)-10 production, were measured pre- and 4-weeks post-vaccination in young adults (n = 79) and older adults randomized to standard- or high-dose inactivated vaccine (n = 612). Circulating tumour necrosis factor (TNF), interleukin (IL)-6 and C-reactive protein (CRP) were also measured pre-vaccination. Post-vaccination antibody titres were significantly associated with systemic inflammatory levels; specifically, IL-6 was positively associated with A/H3N2 titres in young adults (Cohen’s d = 0.36), and in older high-dose, but not standard-dose recipients, all systemic inflammatory mediators were positively associated with A/H1N1, A/H3N2 and B titres (d = 0.10–0.45). We further show that the frequency of ILT2(+)CD57(+) CD56-Dim natural killer (NK)-cells was positively associated with both plasma IL-6 and post-vaccination A/H3N2 titres in a follow-up cohort of older high-dose recipients (n = 63). Pathway analysis suggested that ILT2(+)CD57(+) Dim NK-cells mediated 40% of the association between IL-6 and A/H3N2 titres, which may be related to underlying participant frailty. Conclusions: In summary, our data suggest a complex relationship amongst influenza vaccine responses, systemic inflammation and NK-cell phenotype in older adults, which depends heavily on age, vaccine dose and possibly overall health status. While our results suggest that “inflammaging” may increase vaccine immunogenicity in older adults, it is yet to be determined whether this enhancement contributes to improved protection against influenza disease.

Langue d'origineEnglish
Numéro d'article26
JournalImmunity and Ageing
Volume19
Numéro de publication1
DOI
Statut de publicationPublished - déc. 2022

Note bibliographique

Funding Information:
Funding for this study was generously provided by the Lung Health Foundation through a Team Breathe Award to Dr. Verschoor, while the original trial was funded by the NIA/National Institutes of Health to Drs. Kuchel and McElhaney (R01 AG048023). Dr Haynes and Dr Kuchel are also supported by the Claude D Pepper Older Americans Independence Center at UConn (P30 AG067988). Dr. Verschoor receives support as the Research Lead in Healthy Aging from Health Sciences North Research Institute and the Health Sciences North Volunteer Association, Dr. McElhaney was supported by the Health Sciences North Chair in Healthy Aging, Dr. Kuchel is supported by the Travelers Chair in Geriatrics and Gerontology, and Dr. Loeb is supported by the Michael G DeGroote Chair in Infectious Diseases.

Funding Information:
MKA reports honoraria from Sanofi, Pfizer and Seqirus, and grants from GSK, Sanofi, Pfizer, Merck and the Canadian Frailty Network, outside of the current work. JEM reported payments from RestorBio, Sanofi, GSK, Merck and Medicago outside of the submitted work.

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus Subject Areas

  • Immunology
  • Ageing

PubMed: MeSH publication types

  • Journal Article

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