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A Fourth Dose of COVID-19 Vaccine Does Not Induce Neutralization of the Omicron Variant Among Solid Organ Transplant Recipients With Suboptimal Vaccine Response
Humoral responses to coronavirus disease 2019 (COVID-19) vaccines are attenuated in solid organ transplant recipients (SOTRs), necessitating additional booster vaccinations. The Omicron variant demonstrates substantial immune evasion, and it is unknown whether additional vaccine doses increase neutr...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213052/ https://www.ncbi.nlm.nih.gov/pubmed/35417115 http://dx.doi.org/10.1097/TP.0000000000004140 |
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author | Karaba, Andrew H. Johnston, Trevor S. Aytenfisu, Tihitina Y. Akinde, Olivia Eby, Yolanda Ruff, Jessica E. Abedon, Aura T. Alejo, Jennifer L. Blankson, Joel N. Cox, Andrea L. Bailey, Justin R. Klein, Sabra L. Pekosz, Andrew Segev, Dorry L. Tobian, Aaron A.R. Werbel, William A. |
author_facet | Karaba, Andrew H. Johnston, Trevor S. Aytenfisu, Tihitina Y. Akinde, Olivia Eby, Yolanda Ruff, Jessica E. Abedon, Aura T. Alejo, Jennifer L. Blankson, Joel N. Cox, Andrea L. Bailey, Justin R. Klein, Sabra L. Pekosz, Andrew Segev, Dorry L. Tobian, Aaron A.R. Werbel, William A. |
author_sort | Karaba, Andrew H. |
collection | PubMed |
description | Humoral responses to coronavirus disease 2019 (COVID-19) vaccines are attenuated in solid organ transplant recipients (SOTRs), necessitating additional booster vaccinations. The Omicron variant demonstrates substantial immune evasion, and it is unknown whether additional vaccine doses increase neutralizing capacity versus this variant of concern (VOC) among SOTRs. METHODS. Within an observational cohort, 25 SOTRs with low seroresponse underwent anti–severe acute respiratory syndrome coronavirus 2 spike and receptor-binding domain immunoglobulin (Ig)G testing using a commercially available multiplex ELISA before and after a fourth COVID-19 vaccine dose (D4). Surrogate neutralization (percent angiotensin-converting enzyme 2 inhibition [%ACE2i], range 0%–100% with >20% correlating with live virus neutralization) was measured against full-length spike proteins of the vaccine strain and 5 VOCs including Delta and Omicron. Changes in IgG level and %ACE2i were compared using the paired Wilcoxon signed-rank test. RESULTS. Anti–receptor-binding domain and anti-spike seropositivity increased post-D4 from 56% to 84% and 68% to 88%, respectively. Median (interquartile range) anti-spike antibody significantly increased post-D4 from 42.3 (4.9–134.2) to 228.9 (1115.4–655.8) World Health Organization binding antibody units. %ACE2i (median [interquartile range]) also significantly increased against the vaccine strain (5.8% [0%–16.8%] to 20.6% [5.8%–45.9%]) and the Delta variant (9.1% [4.9%–12.8%] to 17.1% [10.3%–31.7%]), yet neutralization versus Omicron was poor, did not increase post-D4 (4.1% [0%–6.9%] to 0.5% [0%–5.7%]), and was significantly lower than boosted healthy controls. CONCLUSIONS. Although a fourth vaccine dose increases anti-spike IgG and neutralizing capacity against many VOCs, some SOTRs may remain at high risk for Omicron infection despite boosting. Thus, additional protective interventions or alternative vaccination strategies should be urgently explored. |
format | Online Article Text |
id | pubmed-9213052 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-92130522022-06-23 A Fourth Dose of COVID-19 Vaccine Does Not Induce Neutralization of the Omicron Variant Among Solid Organ Transplant Recipients With Suboptimal Vaccine Response Karaba, Andrew H. Johnston, Trevor S. Aytenfisu, Tihitina Y. Akinde, Olivia Eby, Yolanda Ruff, Jessica E. Abedon, Aura T. Alejo, Jennifer L. Blankson, Joel N. Cox, Andrea L. Bailey, Justin R. Klein, Sabra L. Pekosz, Andrew Segev, Dorry L. Tobian, Aaron A.R. Werbel, William A. Transplantation Original Clinical Science—General Humoral responses to coronavirus disease 2019 (COVID-19) vaccines are attenuated in solid organ transplant recipients (SOTRs), necessitating additional booster vaccinations. The Omicron variant demonstrates substantial immune evasion, and it is unknown whether additional vaccine doses increase neutralizing capacity versus this variant of concern (VOC) among SOTRs. METHODS. Within an observational cohort, 25 SOTRs with low seroresponse underwent anti–severe acute respiratory syndrome coronavirus 2 spike and receptor-binding domain immunoglobulin (Ig)G testing using a commercially available multiplex ELISA before and after a fourth COVID-19 vaccine dose (D4). Surrogate neutralization (percent angiotensin-converting enzyme 2 inhibition [%ACE2i], range 0%–100% with >20% correlating with live virus neutralization) was measured against full-length spike proteins of the vaccine strain and 5 VOCs including Delta and Omicron. Changes in IgG level and %ACE2i were compared using the paired Wilcoxon signed-rank test. RESULTS. Anti–receptor-binding domain and anti-spike seropositivity increased post-D4 from 56% to 84% and 68% to 88%, respectively. Median (interquartile range) anti-spike antibody significantly increased post-D4 from 42.3 (4.9–134.2) to 228.9 (1115.4–655.8) World Health Organization binding antibody units. %ACE2i (median [interquartile range]) also significantly increased against the vaccine strain (5.8% [0%–16.8%] to 20.6% [5.8%–45.9%]) and the Delta variant (9.1% [4.9%–12.8%] to 17.1% [10.3%–31.7%]), yet neutralization versus Omicron was poor, did not increase post-D4 (4.1% [0%–6.9%] to 0.5% [0%–5.7%]), and was significantly lower than boosted healthy controls. CONCLUSIONS. Although a fourth vaccine dose increases anti-spike IgG and neutralizing capacity against many VOCs, some SOTRs may remain at high risk for Omicron infection despite boosting. Thus, additional protective interventions or alternative vaccination strategies should be urgently explored. Lippincott Williams & Wilkins 2022-04-04 2022-07 /pmc/articles/PMC9213052/ /pubmed/35417115 http://dx.doi.org/10.1097/TP.0000000000004140 Text en Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Original Clinical Science—General Karaba, Andrew H. Johnston, Trevor S. Aytenfisu, Tihitina Y. Akinde, Olivia Eby, Yolanda Ruff, Jessica E. Abedon, Aura T. Alejo, Jennifer L. Blankson, Joel N. Cox, Andrea L. Bailey, Justin R. Klein, Sabra L. Pekosz, Andrew Segev, Dorry L. Tobian, Aaron A.R. Werbel, William A. A Fourth Dose of COVID-19 Vaccine Does Not Induce Neutralization of the Omicron Variant Among Solid Organ Transplant Recipients With Suboptimal Vaccine Response |
title | A Fourth Dose of COVID-19 Vaccine Does Not Induce Neutralization of the Omicron Variant Among Solid Organ Transplant Recipients With Suboptimal Vaccine Response |
title_full | A Fourth Dose of COVID-19 Vaccine Does Not Induce Neutralization of the Omicron Variant Among Solid Organ Transplant Recipients With Suboptimal Vaccine Response |
title_fullStr | A Fourth Dose of COVID-19 Vaccine Does Not Induce Neutralization of the Omicron Variant Among Solid Organ Transplant Recipients With Suboptimal Vaccine Response |
title_full_unstemmed | A Fourth Dose of COVID-19 Vaccine Does Not Induce Neutralization of the Omicron Variant Among Solid Organ Transplant Recipients With Suboptimal Vaccine Response |
title_short | A Fourth Dose of COVID-19 Vaccine Does Not Induce Neutralization of the Omicron Variant Among Solid Organ Transplant Recipients With Suboptimal Vaccine Response |
title_sort | fourth dose of covid-19 vaccine does not induce neutralization of the omicron variant among solid organ transplant recipients with suboptimal vaccine response |
topic | Original Clinical Science—General |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213052/ https://www.ncbi.nlm.nih.gov/pubmed/35417115 http://dx.doi.org/10.1097/TP.0000000000004140 |
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