Research Paper|Volume 12, Issue 24|pp 24633—24650

The impact of physical frailty on the response to inactivated influenza vaccine in older adults

Krissy K. Moehling^1,², Bo Zhai³, William E. Schwarzmann⁴, Uma R. Chandran⁴, Marianna Ortiz³, Mary Patricia Nowalk¹, David Nace⁵, Chyongchiou J. Lin^1,⁶, Michael Susick¹, Min Z. Levine⁷, John F. Alcorn³, Richard K. Zimmerman¹

¹Department of Family Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA
²Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15213, USA
³Division of Pulmonary Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15224, USA
⁴Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA 15261, USA
⁵Division of Geriatric Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA
⁶Ohio State University College of Nursing, Columbus, OH 43210, USA
⁷National Center for Immunization and Respiratory Diseases, Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA

* Completed work while at the Department of Family Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA

Received: August 14, 2020Accepted: October 27, 2020Published: December 9, 2020

https://doi.org/10.18632/aging.202207

Copyright: © 2020 Moehling et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Physical frailty’s impact on hemagglutination inhibition antibody titers (HAI) and peripheral blood mononuclear cell (PBMC) transcriptional responses after influenza vaccination is unclear. Physical frailty was assessed using the 5-item Fried frailty phenotype in 168 community- and assisted-living adults ≥55 years of age during an observational study. Blood was drawn before, 3, 7, and 28 days post-vaccination with the 2017-2018 inactivated influenza vaccine. HAI response to the A/H1N1 strain was measured at Days 0 and 28 using seropositivity, seroconversion, log₂ HAI titers, and fold-rise in log₂ HAI titers. RNA sequencing of PBMCs from Days 0, 3 and 7 was measured in 28 participants and compared using pathway analyses. Frailty was not significantly associated with any HAI outcome in multivariable models. Compared with non-frail participants, frail participants expressed decreased cell proliferation, metabolism, antibody production, and interferon signaling genes. Conversely, frail participants showed elevated gene expression in IL-8 signaling, T-cell exhaustion, and oxidative stress pathways compared with non-frail participants. These results suggest that reduced effectiveness of influenza vaccine among older, frail individuals may be attributed to immunosenescence-related changes in PBMCs that are not reflected in antibody levels.