Kinetics and persistence of cellular and humoral immune responses to SARS‐CoV‐2 vaccine in healthcare workers with or without prior COVID‐19

SARS‐CoV‐2 vaccines are highly efficient against severe forms of the disease, hospitalization and death. Nevertheless, insufficient protection against several circulating viral variants might suggest waning immunity and the need for an additional vaccine dose. We conducted a longitudinal study on th...

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Published in:	Journal of cellular and molecular medicine Vol. 26; no. 4; pp. 1293 - 1305
Main Authors:	Chivu‐Economescu, Mihaela, Bleotu, Coralia, Grancea, Camelia, Chiriac, Daniela, Botezatu, Anca, Iancu, Iulia V., Pitica, Ioana, Necula, Laura G., Neagu, Ana, Matei, Lilia, Dragu, Denisa, Sultana, Camelia, Radu, Elena L., Nastasie, Alina, Voicu, Oana, Ataman, Marius, Nedeianu, Saviana, Mambet, Cristina, Diaconu, Carmen C., Ruta, Simona Maria
Format:	Journal Article
Language:	English
Published:	England John Wiley & Sons, Inc 01-02-2022 John Wiley and Sons Inc
Subjects:	Adult Antibodies Antibodies, Neutralizing - blood Antibodies, Neutralizing - immunology Antibodies, Viral - blood Antibodies, Viral - immunology antibody levels BNT162 Vaccine - immunology Clinical trials Coronaviruses COVID-19 COVID-19 - immunology COVID-19 vaccines Enzymes Health care Health Personnel Hospitalization Humans IFN‐γ Immune response (cell-mediated) Immune response (humoral) immune response post‐infection immune response post‐vaccination Immunity, Cellular Immunity, Humoral Immunoassay Immunoglobulin A Immunoglobulin A - blood Immunoglobulin A - immunology Immunoglobulin G Immunoglobulin G - blood Immunoglobulin G - immunology Infections Interferon Interferon-gamma - blood Interferon-gamma - immunology Kinetics Longitudinal Studies Medical personnel Middle Aged mRNA mRNA vaccine mRNA vaccines neutralizing antibodies Original Public health SARS‐CoV‐2 infection Severe acute respiratory syndrome coronavirus 2 Spike Glycoprotein, Coronavirus - immunology spike‐specific CD4+ T cell spike‐specific CD8+ T cell Time Factors Vaccines United States > US Romania Israel spike-specific CD8+ T cell IFN-γ immune response post-infection immune response post-vaccination SARS-CoV-2 infection antibody levels neutralizing antibodies spike-specific CD4+ T cell mRNA vaccine
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Abstract	SARS‐CoV‐2 vaccines are highly efficient against severe forms of the disease, hospitalization and death. Nevertheless, insufficient protection against several circulating viral variants might suggest waning immunity and the need for an additional vaccine dose. We conducted a longitudinal study on the kinetics and persistence of immune responses in healthcare workers vaccinated with two doses of BNT162b2 mRNA vaccine with or without prior SARS‐CoV‐2 infection. No new infections were diagnosed during follow‐up. At 6 months, post‐vaccination or post‐infection, despite a downward trend in the level of anti‐S IgG antibodies, the neutralizing activity does not decrease significantly, remaining higher than 75% (85.14% for subjects with natural infection, 88.82% for vaccinated after prior infection and 78.37% for vaccinated only). In a live‐virus neutralization assay, the highest neutralization titres were present at baseline and at 6 months follow‐up in persons vaccinated after prior infection. Anti‐S IgA levels showed a significant descending trend in vaccinated subjects (p < 0.05) after 14 weeks. Cellular immune responses are present even in vaccinated participants with declining antibody levels (index ratio 1.1–3) or low neutralizing activity (30%–40%) at 6 months, although with lower T‐cell stimulation index (p = 0.046) and IFN‐γ secretion (p = 0.0007) compared to those with preserved humoral responses.
AbstractList	SARS-CoV-2 vaccines are highly efficient against severe forms of the disease, hospitalization and death. Nevertheless, insufficient protection against several circulating viral variants might suggest waning immunity and the need for an additional vaccine dose. We conducted a longitudinal study on the kinetics and persistence of immune responses in healthcare workers vaccinated with two doses of BNT162b2 mRNA vaccine with or without prior SARS-CoV-2 infection. No new infections were diagnosed during follow-up. At 6 months, post-vaccination or post-infection, despite a downward trend in the level of anti-S IgG antibodies, the neutralizing activity does not decrease significantly, remaining higher than 75% (85.14% for subjects with natural infection, 88.82% for vaccinated after prior infection and 78.37% for vaccinated only). In a live-virus neutralization assay, the highest neutralization titres were present at baseline and at 6 months follow-up in persons vaccinated after prior infection. Anti-S IgA levels showed a significant descending trend in vaccinated subjects (p < 0.05) after 14 weeks. Cellular immune responses are present even in vaccinated participants with declining antibody levels (index ratio 1.1-3) or low neutralizing activity (30%-40%) at 6 months, although with lower T-cell stimulation index (p = 0.046) and IFN-γ secretion (p = 0.0007) compared to those with preserved humoral responses. SARS‐CoV‐2 vaccines are highly efficient against severe forms of the disease, hospitalization and death. Nevertheless, insufficient protection against several circulating viral variants might suggest waning immunity and the need for an additional vaccine dose. We conducted a longitudinal study on the kinetics and persistence of immune responses in healthcare workers vaccinated with two doses of BNT162b2 mRNA vaccine with or without prior SARS‐CoV‐2 infection. No new infections were diagnosed during follow‐up. At 6 months, post‐vaccination or post‐infection, despite a downward trend in the level of anti‐S IgG antibodies, the neutralizing activity does not decrease significantly, remaining higher than 75% (85.14% for subjects with natural infection, 88.82% for vaccinated after prior infection and 78.37% for vaccinated only). In a live‐virus neutralization assay, the highest neutralization titres were present at baseline and at 6 months follow‐up in persons vaccinated after prior infection. Anti‐S IgA levels showed a significant descending trend in vaccinated subjects ( p < 0.05) after 14 weeks. Cellular immune responses are present even in vaccinated participants with declining antibody levels (index ratio 1.1–3) or low neutralizing activity (30%–40%) at 6 months, although with lower T‐cell stimulation index ( p = 0.046) and IFN ‐ γ secretion ( p = 0.0007) compared to those with preserved humoral responses. Abstract SARS‐CoV‐2 vaccines are highly efficient against severe forms of the disease, hospitalization and death. Nevertheless, insufficient protection against several circulating viral variants might suggest waning immunity and the need for an additional vaccine dose. We conducted a longitudinal study on the kinetics and persistence of immune responses in healthcare workers vaccinated with two doses of BNT162b2 mRNA vaccine with or without prior SARS‐CoV‐2 infection. No new infections were diagnosed during follow‐up. At 6 months, post‐vaccination or post‐infection, despite a downward trend in the level of anti‐S IgG antibodies, the neutralizing activity does not decrease significantly, remaining higher than 75% (85.14% for subjects with natural infection, 88.82% for vaccinated after prior infection and 78.37% for vaccinated only). In a live‐virus neutralization assay, the highest neutralization titres were present at baseline and at 6 months follow‐up in persons vaccinated after prior infection. Anti‐S IgA levels showed a significant descending trend in vaccinated subjects ( p < 0.05) after 14 weeks. Cellular immune responses are present even in vaccinated participants with declining antibody levels (index ratio 1.1–3) or low neutralizing activity (30%–40%) at 6 months, although with lower T‐cell stimulation index ( p = 0.046) and IFN ‐ γ secretion ( p = 0.0007) compared to those with preserved humoral responses. SARS‐CoV‐2 vaccines are highly efficient against severe forms of the disease, hospitalization and death. Nevertheless, insufficient protection against several circulating viral variants might suggest waning immunity and the need for an additional vaccine dose. We conducted a longitudinal study on the kinetics and persistence of immune responses in healthcare workers vaccinated with two doses of BNT162b2 mRNA vaccine with or without prior SARS‐CoV‐2 infection. No new infections were diagnosed during follow‐up. At 6 months, post‐vaccination or post‐infection, despite a downward trend in the level of anti‐S IgG antibodies, the neutralizing activity does not decrease significantly, remaining higher than 75% (85.14% for subjects with natural infection, 88.82% for vaccinated after prior infection and 78.37% for vaccinated only). In a live‐virus neutralization assay, the highest neutralization titres were present at baseline and at 6 months follow‐up in persons vaccinated after prior infection. Anti‐S IgA levels showed a significant descending trend in vaccinated subjects (p < 0.05) after 14 weeks. Cellular immune responses are present even in vaccinated participants with declining antibody levels (index ratio 1.1–3) or low neutralizing activity (30%–40%) at 6 months, although with lower T‐cell stimulation index (p = 0.046) and IFN‐γ secretion (p = 0.0007) compared to those with preserved humoral responses. SARS-CoV-2 vaccines are highly efficient against severe forms of the disease, hospitalization and death. Nevertheless, insufficient protection against several circulating viral variants might suggest waning immunity and the need for an additional vaccine dose. We conducted a longitudinal study on the kinetics and persistence of immune responses in healthcare workers vaccinated with two doses of BNT162b2 mRNA vaccine with or without prior SARS-CoV-2 infection. No new infections were diagnosed during follow-up. At 6 months, post-vaccination or post-infection, despite a downward trend in the level of anti-S IgG antibodies, the neutralizing activity does not decrease significantly, remaining higher than 75% (85.14% for subjects with natural infection, 88.82% for vaccinated after prior infection and 78.37% for vaccinated only). In a live-virus neutralization assay, the highest neutralization titres were present at baseline and at 6 months follow-up in persons vaccinated after prior infection. Anti-S IgA levels showed a significant descending trend in vaccinated subjects (p < 0.05) after 14 weeks. Cellular immune responses are present even in vaccinated participants with declining antibody levels (index ratio 1.1-3) or low neutralizing activity (30%-40%) at 6 months, although with lower T-cell stimulation index (p = 0.046) and IFN-γ secretion (p = 0.0007) compared to those with preserved humoral responses.SARS-CoV-2 vaccines are highly efficient against severe forms of the disease, hospitalization and death. Nevertheless, insufficient protection against several circulating viral variants might suggest waning immunity and the need for an additional vaccine dose. We conducted a longitudinal study on the kinetics and persistence of immune responses in healthcare workers vaccinated with two doses of BNT162b2 mRNA vaccine with or without prior SARS-CoV-2 infection. No new infections were diagnosed during follow-up. At 6 months, post-vaccination or post-infection, despite a downward trend in the level of anti-S IgG antibodies, the neutralizing activity does not decrease significantly, remaining higher than 75% (85.14% for subjects with natural infection, 88.82% for vaccinated after prior infection and 78.37% for vaccinated only). In a live-virus neutralization assay, the highest neutralization titres were present at baseline and at 6 months follow-up in persons vaccinated after prior infection. Anti-S IgA levels showed a significant descending trend in vaccinated subjects (p < 0.05) after 14 weeks. Cellular immune responses are present even in vaccinated participants with declining antibody levels (index ratio 1.1-3) or low neutralizing activity (30%-40%) at 6 months, although with lower T-cell stimulation index (p = 0.046) and IFN-γ secretion (p = 0.0007) compared to those with preserved humoral responses.
Author	Nedeianu, Saviana Mambet, Cristina Chivu‐Economescu, Mihaela Iancu, Iulia V. Radu, Elena L. Matei, Lilia Necula, Laura G. Ataman, Marius Pitica, Ioana Grancea, Camelia Chiriac, Daniela Voicu, Oana Bleotu, Coralia Dragu, Denisa Diaconu, Carmen C. Ruta, Simona Maria Sultana, Camelia Botezatu, Anca Nastasie, Alina Neagu, Ana
AuthorAffiliation	2 Carol Davila University of Medicine and Pharmacy Bucharest Romania 1 Stefan S. Nicolau Institute of Virology Bucharest Romania 3 Institute for Water Quality and Resource Management TU Wien Vienna Austria
AuthorAffiliation_xml	– name: 3 Institute for Water Quality and Resource Management TU Wien Vienna Austria – name: 2 Carol Davila University of Medicine and Pharmacy Bucharest Romania – name: 1 Stefan S. Nicolau Institute of Virology Bucharest Romania
Author_xml	– sequence: 1 givenname: Mihaela orcidid: 0000-0001-7512-4700 surname: Chivu‐Economescu fullname: Chivu‐Economescu, Mihaela organization: Stefan S. Nicolau Institute of Virology – sequence: 2 givenname: Coralia orcidid: 0000-0002-9031-338X surname: Bleotu fullname: Bleotu, Coralia organization: Stefan S. Nicolau Institute of Virology – sequence: 3 givenname: Camelia surname: Grancea fullname: Grancea, Camelia organization: Stefan S. Nicolau Institute of Virology – sequence: 4 givenname: Daniela surname: Chiriac fullname: Chiriac, Daniela organization: Stefan S. Nicolau Institute of Virology – sequence: 5 givenname: Anca orcidid: 0000-0002-1502-9733 surname: Botezatu fullname: Botezatu, Anca organization: Stefan S. Nicolau Institute of Virology – sequence: 6 givenname: Iulia V. surname: Iancu fullname: Iancu, Iulia V. organization: Stefan S. Nicolau Institute of Virology – sequence: 7 givenname: Ioana surname: Pitica fullname: Pitica, Ioana organization: Stefan S. Nicolau Institute of Virology – sequence: 8 givenname: Laura G. surname: Necula fullname: Necula, Laura G. organization: Stefan S. Nicolau Institute of Virology – sequence: 9 givenname: Ana surname: Neagu fullname: Neagu, Ana organization: Stefan S. Nicolau Institute of Virology – sequence: 10 givenname: Lilia surname: Matei fullname: Matei, Lilia organization: Stefan S. Nicolau Institute of Virology – sequence: 11 givenname: Denisa surname: Dragu fullname: Dragu, Denisa organization: Stefan S. Nicolau Institute of Virology – sequence: 12 givenname: Camelia surname: Sultana fullname: Sultana, Camelia organization: Carol Davila University of Medicine and Pharmacy – sequence: 13 givenname: Elena L. surname: Radu fullname: Radu, Elena L. organization: Institute for Water Quality and Resource Management TU Wien – sequence: 14 givenname: Alina surname: Nastasie fullname: Nastasie, Alina organization: Stefan S. Nicolau Institute of Virology – sequence: 15 givenname: Oana surname: Voicu fullname: Voicu, Oana organization: Stefan S. Nicolau Institute of Virology – sequence: 16 givenname: Marius surname: Ataman fullname: Ataman, Marius organization: Stefan S. Nicolau Institute of Virology – sequence: 17 givenname: Saviana surname: Nedeianu fullname: Nedeianu, Saviana organization: Stefan S. Nicolau Institute of Virology – sequence: 18 givenname: Cristina orcidid: 0000-0001-8495-7704 surname: Mambet fullname: Mambet, Cristina organization: Carol Davila University of Medicine and Pharmacy – sequence: 19 givenname: Carmen C. orcidid: 0000-0002-2259-1425 surname: Diaconu fullname: Diaconu, Carmen C. email: ccdiaconu@yahoo.com, directie@virology.ro organization: Stefan S. Nicolau Institute of Virology – sequence: 20 givenname: Simona Maria surname: Ruta fullname: Ruta, Simona Maria organization: Carol Davila University of Medicine and Pharmacy
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Copyright	2022 The Authors. published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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Keywords	spike-specific CD8+ T cell IFN-γ immune response post-infection immune response post-vaccination SARS-CoV-2 infection antibody levels neutralizing antibodies spike-specific CD4+ T cell mRNA vaccine
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License	Attribution 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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Snippet	SARS‐CoV‐2 vaccines are highly efficient against severe forms of the disease, hospitalization and death. Nevertheless, insufficient protection against several... SARS-CoV-2 vaccines are highly efficient against severe forms of the disease, hospitalization and death. Nevertheless, insufficient protection against several... Abstract SARS‐CoV‐2 vaccines are highly efficient against severe forms of the disease, hospitalization and death. Nevertheless, insufficient protection against...
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SubjectTerms	Adult Antibodies Antibodies, Neutralizing - blood Antibodies, Neutralizing - immunology Antibodies, Viral - blood Antibodies, Viral - immunology antibody levels BNT162 Vaccine - immunology Clinical trials Coronaviruses COVID-19 COVID-19 - immunology COVID-19 vaccines Enzymes Health care Health Personnel Hospitalization Humans IFN‐γ Immune response (cell-mediated) Immune response (humoral) immune response post‐infection immune response post‐vaccination Immunity, Cellular Immunity, Humoral Immunoassay Immunoglobulin A Immunoglobulin A - blood Immunoglobulin A - immunology Immunoglobulin G Immunoglobulin G - blood Immunoglobulin G - immunology Infections Interferon Interferon-gamma - blood Interferon-gamma - immunology Kinetics Longitudinal Studies Medical personnel Middle Aged mRNA mRNA vaccine mRNA vaccines neutralizing antibodies Original Public health SARS‐CoV‐2 infection Severe acute respiratory syndrome coronavirus 2 Spike Glycoprotein, Coronavirus - immunology spike‐specific CD4+ T cell spike‐specific CD8+ T cell Time Factors Vaccines
Title	Kinetics and persistence of cellular and humoral immune responses to SARS‐CoV‐2 vaccine in healthcare workers with or without prior COVID‐19
URI	https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fjcmm.17186 https://www.ncbi.nlm.nih.gov/pubmed/35043552 https://www.proquest.com/docview/2627313998 https://www.proquest.com/docview/2621250851 https://pubmed.ncbi.nlm.nih.gov/PMC8831971
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