Evaluation of humoral and cellular immune responses in healthcare workers with varying levels of SARS-CoV-2 exposure: effects of CoronaVac vaccination followed by heterologous booster

BackgroundThe COVID-19 pandemic demanded diverse vaccination strategies, and there is significant interest in their effectiveness in generating a robust immune response. In Brazil, the use of CoronaVac was crucial in reducing mortality; however, heterologous booster doses were necessary to enhance m...

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Main Authors: Shayane Martins Rodrigues Gomes, Marcelo Ribeiro-Alves, Roberto Stefan de Almeida Ribeiro, Andréia Carolinne de Souza Brito, Vinicius da Cunha Lisboa, Samara Galdino de Azevedo, Jeane de Souza Nogueira, Leda dos Reis Castilho, Luís Cristóvão Sobrino Pôrto, Silvia Amaral Gonçalves da Silva, Patrícia Maria Lourenço Dutra, Wânia Ferraz Pereira Manfro, Luciana Silva Rodrigues
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Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1576430/full
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author Shayane Martins Rodrigues Gomes
Marcelo Ribeiro-Alves
Roberto Stefan de Almeida Ribeiro
Andréia Carolinne de Souza Brito
Vinicius da Cunha Lisboa
Samara Galdino de Azevedo
Jeane de Souza Nogueira
Leda dos Reis Castilho
Luís Cristóvão Sobrino Pôrto
Silvia Amaral Gonçalves da Silva
Patrícia Maria Lourenço Dutra
Wânia Ferraz Pereira Manfro
Luciana Silva Rodrigues
author_facet Shayane Martins Rodrigues Gomes
Marcelo Ribeiro-Alves
Roberto Stefan de Almeida Ribeiro
Andréia Carolinne de Souza Brito
Vinicius da Cunha Lisboa
Samara Galdino de Azevedo
Jeane de Souza Nogueira
Leda dos Reis Castilho
Luís Cristóvão Sobrino Pôrto
Silvia Amaral Gonçalves da Silva
Patrícia Maria Lourenço Dutra
Wânia Ferraz Pereira Manfro
Luciana Silva Rodrigues
author_sort Shayane Martins Rodrigues Gomes
collection DOAJ
description BackgroundThe COVID-19 pandemic demanded diverse vaccination strategies, and there is significant interest in their effectiveness in generating a robust immune response. In Brazil, the use of CoronaVac was crucial in reducing mortality; however, heterologous booster doses were necessary to enhance memory immune response. This study aimed to evaluate the humoral and cellular immunity in healthcare workers who were vaccinated with a complete regimen of CoronaVac and subsequently received heterologous booster doses over nearly one year.MethodsA longitudinal study recruited healthcare professionals with varying levels of exposure to SARS-CoV-2 from the Health Complex of the Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil. Blood samples were collected at five time points, including baseline and after vaccination with CoronaVac and heterologous booster doses (ChAdOx1 nCov-19 or BNT162b2). The Th1/Th2/Th17 cytokine production was measured by Flow Cytometry, using whole blood samples stimulated or not with the SARS-CoV-2 Spike protein. In parallel, serum levels of IgG antibodies against Spike (anti-S) and Nucleocapsid (anti-N) proteins were assessed using an immunoassay. Adjustments were made for confounding factors, including age, sex, level of SARS-CoV-2 exposure, and COVID-19 infection status.ResultsOur results demonstrate that CoronaVac induced high anti-S IgG levels at all evaluated time points (P<0.01). Cytokine analysis revealed a sustained production of antigen-specific Th1 cytokines, including IL-2 (P<0.01) and IFN-γ (P<0.05) regardless of level of SARS-CoV-2 exposure or previous COVID-19 infection at any point during the study. Additionally, we identified six moderate to strong positive correlations (P<0.0001): IL-10 and IFN-γ (ρ=0.77), IL-6 and TNF (ρ=0.77), IL-2 and IFN-γ (ρ=0.71), IL-6 and IL-10 (ρ=0.66), anti-N IgG and anti-S IgG (ρ=0.62), and IL-2 and anti-S IgG (ρ=0.62).ConclusionThe CoronaVac elicited an antigen-specific cellular immune response, characterized by enhancing the production of key cytokines such as IFN-γ and IL-2, with high levels of anti-S IgG. Furthermore, the administration of heterologous boosters significantly enhanced these immune responses, demonstrating induced-specific immunological response. These findings underscore the importance of primary vaccination and boosters in inducing immune protection against COVID-19, potentially informing future vaccination policies and approaches.
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spelling doaj-art-64d6ad2fa8b94399b6e5e591637ba7c32025-08-20T03:52:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15764301576430Evaluation of humoral and cellular immune responses in healthcare workers with varying levels of SARS-CoV-2 exposure: effects of CoronaVac vaccination followed by heterologous boosterShayane Martins Rodrigues Gomes0Marcelo Ribeiro-Alves1Roberto Stefan de Almeida Ribeiro2Andréia Carolinne de Souza Brito3Vinicius da Cunha Lisboa4Samara Galdino de Azevedo5Jeane de Souza Nogueira6Leda dos Reis Castilho7Luís Cristóvão Sobrino Pôrto8Silvia Amaral Gonçalves da Silva9Patrícia Maria Lourenço Dutra10Wânia Ferraz Pereira Manfro11Luciana Silva Rodrigues12Discipline of Parasitology, Department of Microbiology, Immunology and Parasitology, Medical Science Faculty, Rio de Janeiro State University (UERJ), Rio de Janeiro, BrazilLaboratory of Clinical Research on ISTs/AIDS, National Institute of Infectology Evandro Chagas, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, BrazilLaboratory of Immunopathology (LIP), Discipline of General Pathology, Medical Science Faculty, UERJ, Rio de Janeiro, BrazilDiscipline of Parasitology, Department of Microbiology, Immunology and Parasitology, Medical Science Faculty, Rio de Janeiro State University (UERJ), Rio de Janeiro, BrazilLaboratory of Immunopathology (LIP), Discipline of General Pathology, Medical Science Faculty, UERJ, Rio de Janeiro, BrazilLaboratory of Immunopathology (LIP), Discipline of General Pathology, Medical Science Faculty, UERJ, Rio de Janeiro, BrazilLaboratory of Histocompatibility and Cryopreservation, Tissue Repair and Histocompatibility Technologic Core, Rio de Janeiro State University, Rio de Janeiro, BrazilCell Culture Engineering Lab, Chemical Engineering Program, Coordination of Graduate Engineering Programs, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilLaboratory of Histocompatibility and Cryopreservation, Tissue Repair and Histocompatibility Technologic Core, Rio de Janeiro State University, Rio de Janeiro, BrazilDiscipline of Parasitology, Department of Microbiology, Immunology and Parasitology, Medical Science Faculty, Rio de Janeiro State University (UERJ), Rio de Janeiro, BrazilDiscipline of Parasitology, Department of Microbiology, Immunology and Parasitology, Medical Science Faculty, Rio de Janeiro State University (UERJ), Rio de Janeiro, BrazilDiscipline of Microbiology and Immunology, Department of Microbiology, Immunology and Parasitology, Medical Science Faculty, UERJ, Rio de Janeiro, BrazilLaboratory of Immunopathology (LIP), Discipline of General Pathology, Medical Science Faculty, UERJ, Rio de Janeiro, BrazilBackgroundThe COVID-19 pandemic demanded diverse vaccination strategies, and there is significant interest in their effectiveness in generating a robust immune response. In Brazil, the use of CoronaVac was crucial in reducing mortality; however, heterologous booster doses were necessary to enhance memory immune response. This study aimed to evaluate the humoral and cellular immunity in healthcare workers who were vaccinated with a complete regimen of CoronaVac and subsequently received heterologous booster doses over nearly one year.MethodsA longitudinal study recruited healthcare professionals with varying levels of exposure to SARS-CoV-2 from the Health Complex of the Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil. Blood samples were collected at five time points, including baseline and after vaccination with CoronaVac and heterologous booster doses (ChAdOx1 nCov-19 or BNT162b2). The Th1/Th2/Th17 cytokine production was measured by Flow Cytometry, using whole blood samples stimulated or not with the SARS-CoV-2 Spike protein. In parallel, serum levels of IgG antibodies against Spike (anti-S) and Nucleocapsid (anti-N) proteins were assessed using an immunoassay. Adjustments were made for confounding factors, including age, sex, level of SARS-CoV-2 exposure, and COVID-19 infection status.ResultsOur results demonstrate that CoronaVac induced high anti-S IgG levels at all evaluated time points (P<0.01). Cytokine analysis revealed a sustained production of antigen-specific Th1 cytokines, including IL-2 (P<0.01) and IFN-γ (P<0.05) regardless of level of SARS-CoV-2 exposure or previous COVID-19 infection at any point during the study. Additionally, we identified six moderate to strong positive correlations (P<0.0001): IL-10 and IFN-γ (ρ=0.77), IL-6 and TNF (ρ=0.77), IL-2 and IFN-γ (ρ=0.71), IL-6 and IL-10 (ρ=0.66), anti-N IgG and anti-S IgG (ρ=0.62), and IL-2 and anti-S IgG (ρ=0.62).ConclusionThe CoronaVac elicited an antigen-specific cellular immune response, characterized by enhancing the production of key cytokines such as IFN-γ and IL-2, with high levels of anti-S IgG. Furthermore, the administration of heterologous boosters significantly enhanced these immune responses, demonstrating induced-specific immunological response. These findings underscore the importance of primary vaccination and boosters in inducing immune protection against COVID-19, potentially informing future vaccination policies and approaches.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1576430/fullCoronaVachumoral immunitycytokinesheterologous boosterhealthcare workers
spellingShingle Shayane Martins Rodrigues Gomes
Marcelo Ribeiro-Alves
Roberto Stefan de Almeida Ribeiro
Andréia Carolinne de Souza Brito
Vinicius da Cunha Lisboa
Samara Galdino de Azevedo
Jeane de Souza Nogueira
Leda dos Reis Castilho
Luís Cristóvão Sobrino Pôrto
Silvia Amaral Gonçalves da Silva
Patrícia Maria Lourenço Dutra
Wânia Ferraz Pereira Manfro
Luciana Silva Rodrigues
Evaluation of humoral and cellular immune responses in healthcare workers with varying levels of SARS-CoV-2 exposure: effects of CoronaVac vaccination followed by heterologous booster
Frontiers in Immunology
CoronaVac
humoral immunity
cytokines
heterologous booster
healthcare workers
title Evaluation of humoral and cellular immune responses in healthcare workers with varying levels of SARS-CoV-2 exposure: effects of CoronaVac vaccination followed by heterologous booster
title_full Evaluation of humoral and cellular immune responses in healthcare workers with varying levels of SARS-CoV-2 exposure: effects of CoronaVac vaccination followed by heterologous booster
title_fullStr Evaluation of humoral and cellular immune responses in healthcare workers with varying levels of SARS-CoV-2 exposure: effects of CoronaVac vaccination followed by heterologous booster
title_full_unstemmed Evaluation of humoral and cellular immune responses in healthcare workers with varying levels of SARS-CoV-2 exposure: effects of CoronaVac vaccination followed by heterologous booster
title_short Evaluation of humoral and cellular immune responses in healthcare workers with varying levels of SARS-CoV-2 exposure: effects of CoronaVac vaccination followed by heterologous booster
title_sort evaluation of humoral and cellular immune responses in healthcare workers with varying levels of sars cov 2 exposure effects of coronavac vaccination followed by heterologous booster
topic CoronaVac
humoral immunity
cytokines
heterologous booster
healthcare workers
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1576430/full
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