Obesity and Sex Affect the Immune Responses to Tick-Borne Encephalitis Booster Vaccination
Obesity has dramatically increased over the last 30 years and reaches according to World Health Organization dimensions of a global epidemic. The obesity-associated chronic low-level inflammation contributes to severe comorbidities and directly affects many immune cells leading to immune dysfunction...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2020-05-01
|
Series: | Frontiers in Immunology |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00860/full |
id |
doaj-55907bf668fc4741a99a377d184003e4 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Erika Garner-Spitzer Eva-Maria Poellabauer Angelika Wagner Angela Guzek Ines Zwazl Claudia Seidl-Friedrich Christoph J. Binder Karin Stiasny Michael Kundi Ursula Wiedermann |
spellingShingle |
Erika Garner-Spitzer Eva-Maria Poellabauer Angelika Wagner Angela Guzek Ines Zwazl Claudia Seidl-Friedrich Christoph J. Binder Karin Stiasny Michael Kundi Ursula Wiedermann Obesity and Sex Affect the Immune Responses to Tick-Borne Encephalitis Booster Vaccination Frontiers in Immunology obesity immune dysfunction vaccination tick-borne encephalitis sex metabolism |
author_facet |
Erika Garner-Spitzer Eva-Maria Poellabauer Angelika Wagner Angela Guzek Ines Zwazl Claudia Seidl-Friedrich Christoph J. Binder Karin Stiasny Michael Kundi Ursula Wiedermann |
author_sort |
Erika Garner-Spitzer |
title |
Obesity and Sex Affect the Immune Responses to Tick-Borne Encephalitis Booster Vaccination |
title_short |
Obesity and Sex Affect the Immune Responses to Tick-Borne Encephalitis Booster Vaccination |
title_full |
Obesity and Sex Affect the Immune Responses to Tick-Borne Encephalitis Booster Vaccination |
title_fullStr |
Obesity and Sex Affect the Immune Responses to Tick-Borne Encephalitis Booster Vaccination |
title_full_unstemmed |
Obesity and Sex Affect the Immune Responses to Tick-Borne Encephalitis Booster Vaccination |
title_sort |
obesity and sex affect the immune responses to tick-borne encephalitis booster vaccination |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-05-01 |
description |
Obesity has dramatically increased over the last 30 years and reaches according to World Health Organization dimensions of a global epidemic. The obesity-associated chronic low-level inflammation contributes to severe comorbidities and directly affects many immune cells leading to immune dysfunction and increased susceptibility to infections. Thus, prophylaxis against vaccine-preventable diseases is crucial, yet the responsiveness to several vaccines is unclear under obesity. In order to assess the responsiveness to tick-borne encephalitis (TBE) vaccine, we revaccinated 37 obese individuals and 36 normal-weight controls with a licensed TBE vaccine. Metabolic, hormonal, and immunologic profiles along with vaccine-specific humoral and cellular immune responses were evaluated in sera and peripheral blood mononuclear cells (PBMCs) before, 1 week, 4 weeks, and 6 months after TBE booster. Obese adults had significantly increased metabolic (triglycerides, cholesterol ratios, leptin, insulin) and proinflammatory (C-reactive protein) parameters. They showed stronger initial increase of TBE-specific Ab titers (d7_d28) followed by a significantly faster decline after 6 months, which correlated with high body mass index and leptin and insulin levels. The fold increase of Ab-titer levels was significantly higher in obese compared to control males and linked to reduced testosterone levels. Obesity also affected cellular responses: PBMCs of the obese vaccinees had elevated interleukin 2 and interferon γ levels upon antigen stimulation, indicating a leptin-dependent proinflammatory TH1 polarization. The expansion of total and naive B cells in obese might explain the initial increase of Ab titers, whereas the reduced B-memory cell and plasma blast generation could be related to fast Ab decline with a limited maintenance of titers. Among T follicular helper cell (Tfh) cells, the Tfh17 subset was significantly expanded particularly in obese males, where we observed a strong initial Ab increase. Systemic but not local vaccine side effects were more frequent in obese subjects as a possible consequence of their low-grade proinflammatory state. In summary, TBE booster vaccination was effective in obese individuals, yet the faster Ab decline could result in a reduced long-term protection. The sex-based differences in vaccine responses indicate a complex interplay of the endocrine, metabolic, and immune system during obesity. Further studies on the long-term protection after vaccination are ongoing, and also evaluation of primary vaccination against TBE in obese individuals is planned.Clinical Trial Registration: NCT04017052; https://clinicaltrials.gov/ct2/show/NCT04017052. |
topic |
obesity immune dysfunction vaccination tick-borne encephalitis sex metabolism |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.00860/full |
work_keys_str_mv |
AT erikagarnerspitzer obesityandsexaffecttheimmuneresponsestotickborneencephalitisboostervaccination AT evamariapoellabauer obesityandsexaffecttheimmuneresponsestotickborneencephalitisboostervaccination AT angelikawagner obesityandsexaffecttheimmuneresponsestotickborneencephalitisboostervaccination AT angelaguzek obesityandsexaffecttheimmuneresponsestotickborneencephalitisboostervaccination AT ineszwazl obesityandsexaffecttheimmuneresponsestotickborneencephalitisboostervaccination AT claudiaseidlfriedrich obesityandsexaffecttheimmuneresponsestotickborneencephalitisboostervaccination AT christophjbinder obesityandsexaffecttheimmuneresponsestotickborneencephalitisboostervaccination AT karinstiasny obesityandsexaffecttheimmuneresponsestotickborneencephalitisboostervaccination AT michaelkundi obesityandsexaffecttheimmuneresponsestotickborneencephalitisboostervaccination AT ursulawiedermann obesityandsexaffecttheimmuneresponsestotickborneencephalitisboostervaccination |
_version_ |
1724681546702520320 |
spelling |
doaj-55907bf668fc4741a99a377d184003e42020-11-25T03:04:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-05-011110.3389/fimmu.2020.00860531546Obesity and Sex Affect the Immune Responses to Tick-Borne Encephalitis Booster VaccinationErika Garner-Spitzer0Eva-Maria Poellabauer1Angelika Wagner2Angela Guzek3Ines Zwazl4Claudia Seidl-Friedrich5Christoph J. Binder6Karin Stiasny7Michael Kundi8Ursula Wiedermann9Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, AustriaInstitute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, AustriaInstitute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, AustriaInstitute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, AustriaInstitute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, AustriaInstitute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, AustriaDepartment for Laboratory Medicine, Medical University Vienna, Vienna, AustriaCenter of Virology, Medical University Vienna, Vienna, AustriaCenter for Public Health, Medical University Vienna, Vienna, AustriaInstitute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, AustriaObesity has dramatically increased over the last 30 years and reaches according to World Health Organization dimensions of a global epidemic. The obesity-associated chronic low-level inflammation contributes to severe comorbidities and directly affects many immune cells leading to immune dysfunction and increased susceptibility to infections. Thus, prophylaxis against vaccine-preventable diseases is crucial, yet the responsiveness to several vaccines is unclear under obesity. In order to assess the responsiveness to tick-borne encephalitis (TBE) vaccine, we revaccinated 37 obese individuals and 36 normal-weight controls with a licensed TBE vaccine. Metabolic, hormonal, and immunologic profiles along with vaccine-specific humoral and cellular immune responses were evaluated in sera and peripheral blood mononuclear cells (PBMCs) before, 1 week, 4 weeks, and 6 months after TBE booster. Obese adults had significantly increased metabolic (triglycerides, cholesterol ratios, leptin, insulin) and proinflammatory (C-reactive protein) parameters. They showed stronger initial increase of TBE-specific Ab titers (d7_d28) followed by a significantly faster decline after 6 months, which correlated with high body mass index and leptin and insulin levels. The fold increase of Ab-titer levels was significantly higher in obese compared to control males and linked to reduced testosterone levels. Obesity also affected cellular responses: PBMCs of the obese vaccinees had elevated interleukin 2 and interferon γ levels upon antigen stimulation, indicating a leptin-dependent proinflammatory TH1 polarization. The expansion of total and naive B cells in obese might explain the initial increase of Ab titers, whereas the reduced B-memory cell and plasma blast generation could be related to fast Ab decline with a limited maintenance of titers. Among T follicular helper cell (Tfh) cells, the Tfh17 subset was significantly expanded particularly in obese males, where we observed a strong initial Ab increase. Systemic but not local vaccine side effects were more frequent in obese subjects as a possible consequence of their low-grade proinflammatory state. In summary, TBE booster vaccination was effective in obese individuals, yet the faster Ab decline could result in a reduced long-term protection. The sex-based differences in vaccine responses indicate a complex interplay of the endocrine, metabolic, and immune system during obesity. Further studies on the long-term protection after vaccination are ongoing, and also evaluation of primary vaccination against TBE in obese individuals is planned.Clinical Trial Registration: NCT04017052; https://clinicaltrials.gov/ct2/show/NCT04017052.https://www.frontiersin.org/article/10.3389/fimmu.2020.00860/fullobesityimmune dysfunctionvaccinationtick-borne encephalitissexmetabolism |