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Cellular and Humoral Immune Responses and Breakthrough Infections After Two Doses of BNT162b Vaccine in Healthcare Workers (HW) 180 Days After the Second Vaccine Dose
BACKGROUND: Immunity and clinical protection induced by mRNA vaccines against SARS-CoV-2 have been shown to decline overtime. To gather information on the immunity profile deemed sufficient in protecting against hospitalization, we tested IgG levels, interferon-gamma (IFN-γ) secretion, and neutraliz...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008351/ https://www.ncbi.nlm.nih.gov/pubmed/35433614 http://dx.doi.org/10.3389/fpubh.2022.847384 |
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author | Mangia, Alessandra Serra, Nicola Cocomazzi, Giovanna Giambra, Vincenzo Antinucci, Stefano Maiorana, Alberto Giuliani, Francesco Montomoli, Emanuele Cantaloni, Paolo Manenti, Alessandro Piazzolla, Valeria |
author_facet | Mangia, Alessandra Serra, Nicola Cocomazzi, Giovanna Giambra, Vincenzo Antinucci, Stefano Maiorana, Alberto Giuliani, Francesco Montomoli, Emanuele Cantaloni, Paolo Manenti, Alessandro Piazzolla, Valeria |
author_sort | Mangia, Alessandra |
collection | PubMed |
description | BACKGROUND: Immunity and clinical protection induced by mRNA vaccines against SARS-CoV-2 have been shown to decline overtime. To gather information on the immunity profile deemed sufficient in protecting against hospitalization, we tested IgG levels, interferon-gamma (IFN-γ) secretion, and neutralizing antibodies 180 days (d180) after the second shot of BNT162b vaccine, in HW. METHODS: A total of 392 subjects were enrolled. All received BioNTech/Pfizer from February 2020 to April 2021. The vaccine-specific humoral response was quantitatively determined by testing for IgG anti-S1 domain of SARS-CoV-spike protein. Live virus microneutralization (MN) was evaluated by an assay performing incubation of serial 2-fold dilution of human serum samples, starting from 1:10 to 1:5120, with an equal volume of Wuhan strain and Delta VOC viral solution and assessing the presence/absence of a cytopathic effect. SARS-CoV-2-spike protein-specific T-cell response was determined by a commercial IFN-γ release assay. RESULTS: In 352 individuals, at d180, IgG levels decreased substantially but no results below the assay's positivity threshold were observed. Overall, 22 naive (8.1%) had values above the highest threshold. Among COVID-naive, the impact of age, which was observed at earlier stages, disappeared at d180, while it remained significant for 81 who had experienced a previous infection. Following the predictive model of protection by Khoury, we transformed the neutralizing titers in IU/ml and used a 54 IU/ml threshold to identify subjects with 50% protective immunity. Overall, live virus MN showed almost all subjects with previous exposure to SARS-CoV-2 neutralized the virus as compared to 33% of naive double-dosed subjects (p < 0.0001). All previously exposed subjects had strong IFN-γ secretion (>200 mIU/ml); among 271 naive, 7 (2.58%) and 17 (6.27%) subjects did not show borderline or strong secretion, respectively. CONCLUSIONS: In naive subjects, low IgG titers are relatively long-lasting. Only a third of naive subjects maintain neutralizing responses. After specific stimulation, a very limited number of naive were unable to produce IFN-γ. The results attained in the small group of subjects with breakthrough infection suggest that simultaneous neutralizing antibody titers <20, binding antibody levels/ml <200, and IFN-γ <1,000 mIU/ml in subjects older than 58 may identify at-risk groups. |
format | Online Article Text |
id | pubmed-9008351 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90083512022-04-15 Cellular and Humoral Immune Responses and Breakthrough Infections After Two Doses of BNT162b Vaccine in Healthcare Workers (HW) 180 Days After the Second Vaccine Dose Mangia, Alessandra Serra, Nicola Cocomazzi, Giovanna Giambra, Vincenzo Antinucci, Stefano Maiorana, Alberto Giuliani, Francesco Montomoli, Emanuele Cantaloni, Paolo Manenti, Alessandro Piazzolla, Valeria Front Public Health Public Health BACKGROUND: Immunity and clinical protection induced by mRNA vaccines against SARS-CoV-2 have been shown to decline overtime. To gather information on the immunity profile deemed sufficient in protecting against hospitalization, we tested IgG levels, interferon-gamma (IFN-γ) secretion, and neutralizing antibodies 180 days (d180) after the second shot of BNT162b vaccine, in HW. METHODS: A total of 392 subjects were enrolled. All received BioNTech/Pfizer from February 2020 to April 2021. The vaccine-specific humoral response was quantitatively determined by testing for IgG anti-S1 domain of SARS-CoV-spike protein. Live virus microneutralization (MN) was evaluated by an assay performing incubation of serial 2-fold dilution of human serum samples, starting from 1:10 to 1:5120, with an equal volume of Wuhan strain and Delta VOC viral solution and assessing the presence/absence of a cytopathic effect. SARS-CoV-2-spike protein-specific T-cell response was determined by a commercial IFN-γ release assay. RESULTS: In 352 individuals, at d180, IgG levels decreased substantially but no results below the assay's positivity threshold were observed. Overall, 22 naive (8.1%) had values above the highest threshold. Among COVID-naive, the impact of age, which was observed at earlier stages, disappeared at d180, while it remained significant for 81 who had experienced a previous infection. Following the predictive model of protection by Khoury, we transformed the neutralizing titers in IU/ml and used a 54 IU/ml threshold to identify subjects with 50% protective immunity. Overall, live virus MN showed almost all subjects with previous exposure to SARS-CoV-2 neutralized the virus as compared to 33% of naive double-dosed subjects (p < 0.0001). All previously exposed subjects had strong IFN-γ secretion (>200 mIU/ml); among 271 naive, 7 (2.58%) and 17 (6.27%) subjects did not show borderline or strong secretion, respectively. CONCLUSIONS: In naive subjects, low IgG titers are relatively long-lasting. Only a third of naive subjects maintain neutralizing responses. After specific stimulation, a very limited number of naive were unable to produce IFN-γ. The results attained in the small group of subjects with breakthrough infection suggest that simultaneous neutralizing antibody titers <20, binding antibody levels/ml <200, and IFN-γ <1,000 mIU/ml in subjects older than 58 may identify at-risk groups. Frontiers Media S.A. 2022-03-31 /pmc/articles/PMC9008351/ /pubmed/35433614 http://dx.doi.org/10.3389/fpubh.2022.847384 Text en Copyright © 2022 Mangia, Serra, Cocomazzi, Giambra, Antinucci, Maiorana, Giuliani, Montomoli, Cantaloni, Manenti and Piazzolla. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Public Health Mangia, Alessandra Serra, Nicola Cocomazzi, Giovanna Giambra, Vincenzo Antinucci, Stefano Maiorana, Alberto Giuliani, Francesco Montomoli, Emanuele Cantaloni, Paolo Manenti, Alessandro Piazzolla, Valeria Cellular and Humoral Immune Responses and Breakthrough Infections After Two Doses of BNT162b Vaccine in Healthcare Workers (HW) 180 Days After the Second Vaccine Dose |
title | Cellular and Humoral Immune Responses and Breakthrough Infections After Two Doses of BNT162b Vaccine in Healthcare Workers (HW) 180 Days After the Second Vaccine Dose |
title_full | Cellular and Humoral Immune Responses and Breakthrough Infections After Two Doses of BNT162b Vaccine in Healthcare Workers (HW) 180 Days After the Second Vaccine Dose |
title_fullStr | Cellular and Humoral Immune Responses and Breakthrough Infections After Two Doses of BNT162b Vaccine in Healthcare Workers (HW) 180 Days After the Second Vaccine Dose |
title_full_unstemmed | Cellular and Humoral Immune Responses and Breakthrough Infections After Two Doses of BNT162b Vaccine in Healthcare Workers (HW) 180 Days After the Second Vaccine Dose |
title_short | Cellular and Humoral Immune Responses and Breakthrough Infections After Two Doses of BNT162b Vaccine in Healthcare Workers (HW) 180 Days After the Second Vaccine Dose |
title_sort | cellular and humoral immune responses and breakthrough infections after two doses of bnt162b vaccine in healthcare workers (hw) 180 days after the second vaccine dose |
topic | Public Health |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008351/ https://www.ncbi.nlm.nih.gov/pubmed/35433614 http://dx.doi.org/10.3389/fpubh.2022.847384 |
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