Proteomic Profiling of Human Peripheral Blood Cell Targets of IgG Induced by SARS-CoV-2: Insights into Vaccine Safety

Background/Objectives: COVID-19 has been associated with a wide range of immune responses, including the production of autoantibodies, particularly in severe cases. This study investigates the IgG autoantibody responses in patients with varying severities of COVID-19 infection and compares these res...

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Main Authors: Nicolle Rakanidis Machado, Lais Alves do Nascimento, Beatriz Oliveira Fagundes, João Vitor da Silva Borges, Fabio da Ressureição Sgnotto, Isabella Siuffi Bergamasco, Juliana Ruiz Fernandes, Thalyta Nery Carvalho Pinto, Anna Julia Pietrobon, Gil Benard, Maria Notomi Sato, Jefferson Russo Victor
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/13/7/694
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author Nicolle Rakanidis Machado
Lais Alves do Nascimento
Beatriz Oliveira Fagundes
João Vitor da Silva Borges
Fabio da Ressureição Sgnotto
Isabella Siuffi Bergamasco
Juliana Ruiz Fernandes
Thalyta Nery Carvalho Pinto
Anna Julia Pietrobon
Gil Benard
Maria Notomi Sato
Jefferson Russo Victor
author_facet Nicolle Rakanidis Machado
Lais Alves do Nascimento
Beatriz Oliveira Fagundes
João Vitor da Silva Borges
Fabio da Ressureição Sgnotto
Isabella Siuffi Bergamasco
Juliana Ruiz Fernandes
Thalyta Nery Carvalho Pinto
Anna Julia Pietrobon
Gil Benard
Maria Notomi Sato
Jefferson Russo Victor
author_sort Nicolle Rakanidis Machado
collection DOAJ
description Background/Objectives: COVID-19 has been associated with a wide range of immune responses, including the production of autoantibodies, particularly in severe cases. This study investigates the IgG autoantibody responses in patients with varying severities of COVID-19 infection and compares these responses with vaccinated individuals. Methods: We utilized proteomic profiling to analyze autoantibody reactivity against a broad spectrum of proteins expressed in lymphoid and myeloid cell subsets in serum samples from severe and moderate COVID-19 patients, as well as vaccinated individuals who received the inactivated CoronaVac (Sinovac) vaccine. Results: Our findings indicate a marked increase in the diversity and number of IgG autoantibodies targeting intracellular and membrane-associated proteins in severe COVID-19 cases, compared to those with moderate cases of the disease. The autoantibody response in severe cases was found to primarily target proteins involved in immune cell activation, signaling, and differentiation, suggesting potential pathways of immune dysregulation and autoimmunity. In contrast, vaccinated individuals did not exhibit similar autoantibody reactivity, pointing to a more controlled immune response post-vaccination. Notably, no significant autoimmune responses were detected in the vaccinated cohort, suggesting that the inactivated vaccine does not induce autoreactive IgG. These findings align with the established safety profile of COVID-19 vaccines, especially in comparison to the heightened immune dysregulation observed in severe COVID-19 patients. The absence of a significant autoantibody response in vaccinated individuals supports the notion that vaccines, while inducing robust immune activation, do not typically trigger autoimmunity in healthy individuals. Conclusions: Our study underscores the importance of distinguishing between the immune responses triggered by infection and vaccination and highlights the need for the continued monitoring of autoimmune responses in severe COVID-19 cases. Future research should focus on the long-term persistence and clinical relevance of these autoantibodies, particularly in individuals with pre-existing autoimmune conditions or genetic predispositions.
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spelling doaj-art-5aeacb6b3f1c46328d2d845d804716ce2025-08-20T03:32:35ZengMDPI AGVaccines2076-393X2025-06-0113769410.3390/vaccines13070694Proteomic Profiling of Human Peripheral Blood Cell Targets of IgG Induced by SARS-CoV-2: Insights into Vaccine SafetyNicolle Rakanidis Machado0Lais Alves do Nascimento1Beatriz Oliveira Fagundes2João Vitor da Silva Borges3Fabio da Ressureição Sgnotto4Isabella Siuffi Bergamasco5Juliana Ruiz Fernandes6Thalyta Nery Carvalho Pinto7Anna Julia Pietrobon8Gil Benard9Maria Notomi Sato10Jefferson Russo Victor11Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of São Paulo, São Paulo 05403-000, BrazilLaboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of São Paulo, São Paulo 05403-000, BrazilLaboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of São Paulo, São Paulo 05403-000, BrazilSchool of Medicine, Santo Amaro University (UNISA), São Paulo 04829-300, BrazilPost Graduation Program in Health Sciences, Santo Amaro University (UNISA), São Paulo 04829-300, BrazilPost Graduation Program in Health Sciences, Santo Amaro University (UNISA), São Paulo 04829-300, BrazilLaboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of São Paulo, São Paulo 05403-000, BrazilLaboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of São Paulo, São Paulo 05403-000, BrazilLaboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of São Paulo, São Paulo 05403-000, BrazilLaboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of São Paulo, São Paulo 05403-000, BrazilLaboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of São Paulo, São Paulo 05403-000, BrazilLaboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of São Paulo, São Paulo 05403-000, BrazilBackground/Objectives: COVID-19 has been associated with a wide range of immune responses, including the production of autoantibodies, particularly in severe cases. This study investigates the IgG autoantibody responses in patients with varying severities of COVID-19 infection and compares these responses with vaccinated individuals. Methods: We utilized proteomic profiling to analyze autoantibody reactivity against a broad spectrum of proteins expressed in lymphoid and myeloid cell subsets in serum samples from severe and moderate COVID-19 patients, as well as vaccinated individuals who received the inactivated CoronaVac (Sinovac) vaccine. Results: Our findings indicate a marked increase in the diversity and number of IgG autoantibodies targeting intracellular and membrane-associated proteins in severe COVID-19 cases, compared to those with moderate cases of the disease. The autoantibody response in severe cases was found to primarily target proteins involved in immune cell activation, signaling, and differentiation, suggesting potential pathways of immune dysregulation and autoimmunity. In contrast, vaccinated individuals did not exhibit similar autoantibody reactivity, pointing to a more controlled immune response post-vaccination. Notably, no significant autoimmune responses were detected in the vaccinated cohort, suggesting that the inactivated vaccine does not induce autoreactive IgG. These findings align with the established safety profile of COVID-19 vaccines, especially in comparison to the heightened immune dysregulation observed in severe COVID-19 patients. The absence of a significant autoantibody response in vaccinated individuals supports the notion that vaccines, while inducing robust immune activation, do not typically trigger autoimmunity in healthy individuals. Conclusions: Our study underscores the importance of distinguishing between the immune responses triggered by infection and vaccination and highlights the need for the continued monitoring of autoimmune responses in severe COVID-19 cases. Future research should focus on the long-term persistence and clinical relevance of these autoantibodies, particularly in individuals with pre-existing autoimmune conditions or genetic predispositions.https://www.mdpi.com/2076-393X/13/7/694IgGCOVID-19autoantibodiesSARS-CoV-2PBMC
spellingShingle Nicolle Rakanidis Machado
Lais Alves do Nascimento
Beatriz Oliveira Fagundes
João Vitor da Silva Borges
Fabio da Ressureição Sgnotto
Isabella Siuffi Bergamasco
Juliana Ruiz Fernandes
Thalyta Nery Carvalho Pinto
Anna Julia Pietrobon
Gil Benard
Maria Notomi Sato
Jefferson Russo Victor
Proteomic Profiling of Human Peripheral Blood Cell Targets of IgG Induced by SARS-CoV-2: Insights into Vaccine Safety
Vaccines
IgG
COVID-19
autoantibodies
SARS-CoV-2
PBMC
title Proteomic Profiling of Human Peripheral Blood Cell Targets of IgG Induced by SARS-CoV-2: Insights into Vaccine Safety
title_full Proteomic Profiling of Human Peripheral Blood Cell Targets of IgG Induced by SARS-CoV-2: Insights into Vaccine Safety
title_fullStr Proteomic Profiling of Human Peripheral Blood Cell Targets of IgG Induced by SARS-CoV-2: Insights into Vaccine Safety
title_full_unstemmed Proteomic Profiling of Human Peripheral Blood Cell Targets of IgG Induced by SARS-CoV-2: Insights into Vaccine Safety
title_short Proteomic Profiling of Human Peripheral Blood Cell Targets of IgG Induced by SARS-CoV-2: Insights into Vaccine Safety
title_sort proteomic profiling of human peripheral blood cell targets of igg induced by sars cov 2 insights into vaccine safety
topic IgG
COVID-19
autoantibodies
SARS-CoV-2
PBMC
url https://www.mdpi.com/2076-393X/13/7/694
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