Greater activation of peripheral T follicular helper cells following high dose influenza vaccine in older adults forecasts seroconversion |
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| Institution: | 1. Vanderbilt University Medical Center, Department of Internal Medicine, Nashville, TN 38232, United States;2. Vanderbilt University School of Medicine, Department of Pathology, Microbiology and Immunology, Nashville, TN 38232, United States;3. Vanderbilt University Medical Center, Flow Cytometry Shared Resource, Nashville, TN 38232, United States;4. Vanderbilt University Medical Center, Vaccine Research Program, Nashville, TN 38232, United States;1. Merck & Co., Inc., Kenilworth, NJ, USA;2. Canadian Center for Vaccinology, IWK Health Centre and Nova Scotia Health Authority, Dalhousie University, Halifax, NS, Canada;3. Washington University School of Medicine, St. Louis, MO, USA;4. Department of Medicine at Huddinge, Division of Hematology, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden;1. Department of Medical Sciences, Section of Hematology, Uppsala University, Uppsala, Sweden;2. Department of Medicine, Section of Hematology, Örebro University Hospital, Örebro, Sweden;3. Department of Medicine, Falun Hospital, Falun, Sweden;4. Institution of Clinical Sciences, Faculty of Medicine, Lund University Hospital, Lund, Sweden;5. Department of Medicine, Section of Hematology, South Älvsborg Hospital, Borås, Sweden;6. Department of Medicine, Eskilstuna Hospital, Eskilstuna, Sweden;7. Department of Medicine, Karlstad Hospital, Karlstad, Sweden;8. Department of Medicine, Unit of Hematology, Karolinska Institute and Karolinska University Hospital, Huddinge, Sweden;1. Department of Medical Oncology, Clinique Saint Jean, Cagnes-sur-Mer, France;2. Department of Biostatistics and Epidemiology, Centre Antoine Lacassagne, Nice, France;3. Department of Biology, Cerballiance, Cagnes-sur-Mer, France;4. Department of Radiation Oncology, Clinique Saint Jean, Cagnes-sur-Mer, France;5. Department of Infectious Disease, Centre Hospitalo-Universitaire de Nice, Nice, France;1. Department of Oncology and Hematology, Medical Oncology Unit, Central Hospital of Belcolle, Viterbo, Italy;2. Biostatistics Unit, Scientific Directorate, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy;3. Departments of Oncology and Hematology, Microbiology and Virology Unit, Viterbo, Italy;4. Oncology and Hematology, Molecular Biology and Covid Diagnostics, Central Hospital of Belcolle, Viterbo, Italy;1. National Centre for Cell Science, Pune, MH, India;2. Departments of Surgery and Microbiology and Immunology, and Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, United States;3. Institute for Immunology, University of Regensburg, Regensburg, Germany;1. Department of Infectious Diseases, Belarusian State Medical University, Minsk, Belarus;2. Minsk Scientific and Practical Center of Surgery, Transplantology and Hematology, Belarus |
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| Abstract: | BackgroundInfluenza related morbidity and mortality disproportionately impacts older adults. The serologic response to vaccine is diminished in older adults; however, high dose inactivated influenza vaccine (HD IIV) has shown improved rates of seroconversion compared to standard dose (SD IIV). We hypothesize this may be due to the superior ability of high dose vaccine to activate T follicular helper (Tfh) cells and provide B cell dependent T cell help.MethodsWe measured peripheral Tfh (pTfh) activation in 50 community dwelling adults 65 years or older who were randomly assigned to receive either the HD IIV or SD IIV.ResultsThe HD vaccination elicited significantly higher levels of ICOS expression on pTfh cells, at day 7 compared to SD vaccination (p = 0.02). The magnitude of the increase in ICOS+ pTfh cells from baseline to day 7 was predictive of seroconversion for both influenza A and B vaccination.ConclusionStrong Tfh activation in response to influenza vaccination forecasts successful seroconversion in older adults, and HD IIV elicits greater Tfh activation than SD IIV. Future vaccine studies should focus on ways to further optimize the Tfh response. |
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| Keywords: | Influenza vaccine High dose influenza vaccine T follicular helper cells Tfh viSNE |
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