Longitudinal Analyses after COVID-19 Recovery or Prolonged Infection Reveal Unique Immunological Signatures after Repeated Vaccinations

To develop preventive and therapeutic measures against coronavirus disease 2019, the complete characterization of immune response and sustained immune activation following viral infection and vaccination are critical. However, the mechanisms controlling intrapersonal variation in antibody titers aga...

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Main Authors: Daisuke Hisamatsu, Akari Ikeda, Lisa Ito, Yasushi Matsushita, Makoto Hiki, Hirotake Mori, Yoko Tabe, Toshio Naito, Chihiro Akazawa
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/10/11/1815
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author Daisuke Hisamatsu
Akari Ikeda
Lisa Ito
Yasushi Matsushita
Makoto Hiki
Hirotake Mori
Yoko Tabe
Toshio Naito
Chihiro Akazawa
author_facet Daisuke Hisamatsu
Akari Ikeda
Lisa Ito
Yasushi Matsushita
Makoto Hiki
Hirotake Mori
Yoko Tabe
Toshio Naito
Chihiro Akazawa
author_sort Daisuke Hisamatsu
collection DOAJ
description To develop preventive and therapeutic measures against coronavirus disease 2019, the complete characterization of immune response and sustained immune activation following viral infection and vaccination are critical. However, the mechanisms controlling intrapersonal variation in antibody titers against SARS-CoV-2 antigens remain unclear. To gain further insights, we performed a robust molecular and cellular investigation of immune responses in infected, recovered, and vaccinated individuals. We evaluated the serum levels of 29 cytokines and their correlation with neutralizing antibody titer. We investigated memory B-cell response in patients infected with the original SARS-CoV-2 strain or other variants, and in vaccinated individuals. Longitudinal correlation analyses revealed that post-vaccination neutralizing potential was more strongly associated with various serum cytokine levels in recovered patients than in naïve individuals. We found that IL-10, CCL2, CXCL10, and IL-12p40 are candidate biomarkers of serum-neutralizing antibody titer after the vaccination of recovered individuals. We found a similar distribution of virus-specific antibody gene families in triple-vaccinated individuals and a patient with COVID-19 pneumonia for 1 year. Thus, distinct immune responses occur depending on the viral strain and clinical history, suggesting that therapeutic options should be selected on a case-by-case basis. Candidate biomarkers that correlate with repeated vaccination may support the efficacy and safety evaluation systems of mRNA vaccines and lead to the development of novel vaccine strategies.
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spelling doaj.art-567e68e8c9f048248ea5c1882ef40dd12023-11-24T07:13:08ZengMDPI AGVaccines2076-393X2022-10-011011181510.3390/vaccines10111815Longitudinal Analyses after COVID-19 Recovery or Prolonged Infection Reveal Unique Immunological Signatures after Repeated VaccinationsDaisuke Hisamatsu0Akari Ikeda1Lisa Ito2Yasushi Matsushita3Makoto Hiki4Hirotake Mori5Yoko Tabe6Toshio Naito7Chihiro Akazawa8Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, JapanIntractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, JapanIntractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, JapanDepartment of Internal Medicine and Rheumatology, Faculty of Medicine, Juntendo University School of Medicine, Tokyo 113-8421, JapanDepartment of Cardiovascular Biology and Medicine, Juntendo University Faculty of Medicine, Tokyo 113-8421, JapanDepartment of General Medicine, Juntendo University Faculty of Medicine, Tokyo 113-8421, JapanDepartment of Clinical Laboratory Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, JapanDepartment of General Medicine, Juntendo University Faculty of Medicine, Tokyo 113-8421, JapanIntractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, JapanTo develop preventive and therapeutic measures against coronavirus disease 2019, the complete characterization of immune response and sustained immune activation following viral infection and vaccination are critical. However, the mechanisms controlling intrapersonal variation in antibody titers against SARS-CoV-2 antigens remain unclear. To gain further insights, we performed a robust molecular and cellular investigation of immune responses in infected, recovered, and vaccinated individuals. We evaluated the serum levels of 29 cytokines and their correlation with neutralizing antibody titer. We investigated memory B-cell response in patients infected with the original SARS-CoV-2 strain or other variants, and in vaccinated individuals. Longitudinal correlation analyses revealed that post-vaccination neutralizing potential was more strongly associated with various serum cytokine levels in recovered patients than in naïve individuals. We found that IL-10, CCL2, CXCL10, and IL-12p40 are candidate biomarkers of serum-neutralizing antibody titer after the vaccination of recovered individuals. We found a similar distribution of virus-specific antibody gene families in triple-vaccinated individuals and a patient with COVID-19 pneumonia for 1 year. Thus, distinct immune responses occur depending on the viral strain and clinical history, suggesting that therapeutic options should be selected on a case-by-case basis. Candidate biomarkers that correlate with repeated vaccination may support the efficacy and safety evaluation systems of mRNA vaccines and lead to the development of novel vaccine strategies.https://www.mdpi.com/2076-393X/10/11/1815COVID-19cytokineimmunodeficiencyvaccine biomarker
spellingShingle Daisuke Hisamatsu
Akari Ikeda
Lisa Ito
Yasushi Matsushita
Makoto Hiki
Hirotake Mori
Yoko Tabe
Toshio Naito
Chihiro Akazawa
Longitudinal Analyses after COVID-19 Recovery or Prolonged Infection Reveal Unique Immunological Signatures after Repeated Vaccinations
Vaccines
COVID-19
cytokine
immunodeficiency
vaccine biomarker
title Longitudinal Analyses after COVID-19 Recovery or Prolonged Infection Reveal Unique Immunological Signatures after Repeated Vaccinations
title_full Longitudinal Analyses after COVID-19 Recovery or Prolonged Infection Reveal Unique Immunological Signatures after Repeated Vaccinations
title_fullStr Longitudinal Analyses after COVID-19 Recovery or Prolonged Infection Reveal Unique Immunological Signatures after Repeated Vaccinations
title_full_unstemmed Longitudinal Analyses after COVID-19 Recovery or Prolonged Infection Reveal Unique Immunological Signatures after Repeated Vaccinations
title_short Longitudinal Analyses after COVID-19 Recovery or Prolonged Infection Reveal Unique Immunological Signatures after Repeated Vaccinations
title_sort longitudinal analyses after covid 19 recovery or prolonged infection reveal unique immunological signatures after repeated vaccinations
topic COVID-19
cytokine
immunodeficiency
vaccine biomarker
url https://www.mdpi.com/2076-393X/10/11/1815
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