Serological assays for differentiating natural COVID-19 infection from vaccine induced immunity
Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved..
BACKGROUND: Natural SARS-CoV-2 infection may elicit antibodies to a range of viral proteins including non-structural protein ORF8. RNA, adenovirus vectored and sub-unit vaccines expressing SARS-CoV-2 spike would be only expected to elicit S-antibodies and antibodies to distinct domains of nucleocapsid (N) protein may reliably differentiate infection from vaccine-elicited antibody. However, inactivated whole virus vaccines may potentially elicit antibody to wider range of viral proteins, including N protein. We hypothesized that antibody to ORF8 protein will discriminate natural infection from vaccination irrespective of vaccine type.
METHODS: We optimized and validated the anti-ORF8 and anti-N C-terminal domain (NCTD) ELISA assays using sera from pre-pandemic, RT-PCR confirmed natural infection sera and BNT162b2 (BNT) or CoronaVac vaccinees. We then applied these optimized assays to a cohort of blood donor sera collected in April-July 2022 with known vaccination and self-reported infection status.
RESULTS: We optimized cut-off values for the anti-ORF8 and anti-N-CTD IgG ELISA assays using receiver-operating-characteristic (ROC) curves. The sensitivity of the anti-ORF8 and anti-N-CTD ELISA for detecting past infection was 83.2% and 99.3%, respectively. Specificity of anti-ORF8 ELISA was 96.8 % vs. the pre-pandemic cohort or 93% considering the pre-pandemic and vaccine cohorts together. The anti-N-CTD ELISA specificity of 98.9% in the pre-pandemic cohort, 93% in BNT vaccinated and only 4 % in CoronaVac vaccinated cohorts. Anti-N-CTD antibody was longer-lived than anti-ORF8 antibody after natural infection.
CONCLUSIONS: Anti-N-CTD antibody assays provide good discrimination between natural infection and vaccination in BNT162b2 vaccinated individuals. Anti-ORF8 antibody can help discriminate infection from vaccination in either type of vaccine and help estimate infection attack rates (IAR) in communities.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:170 |
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| Enthalten in: |
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology - 170(2024) vom: 01. Feb., Seite 105621 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cheng, Samuel M S [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Viral |
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| Anmerkungen: |
Date Completed 22.01.2024 Date Revised 02.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jcv.2023.105621 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365470236 |
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| 100 | 1 | |a Cheng, Samuel M S |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Serological assays for differentiating natural COVID-19 infection from vaccine induced immunity |
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| 500 | |a Date Completed 22.01.2024 | ||
| 500 | |a Date Revised 02.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND: Natural SARS-CoV-2 infection may elicit antibodies to a range of viral proteins including non-structural protein ORF8. RNA, adenovirus vectored and sub-unit vaccines expressing SARS-CoV-2 spike would be only expected to elicit S-antibodies and antibodies to distinct domains of nucleocapsid (N) protein may reliably differentiate infection from vaccine-elicited antibody. However, inactivated whole virus vaccines may potentially elicit antibody to wider range of viral proteins, including N protein. We hypothesized that antibody to ORF8 protein will discriminate natural infection from vaccination irrespective of vaccine type | ||
| 520 | |a METHODS: We optimized and validated the anti-ORF8 and anti-N C-terminal domain (NCTD) ELISA assays using sera from pre-pandemic, RT-PCR confirmed natural infection sera and BNT162b2 (BNT) or CoronaVac vaccinees. We then applied these optimized assays to a cohort of blood donor sera collected in April-July 2022 with known vaccination and self-reported infection status | ||
| 520 | |a RESULTS: We optimized cut-off values for the anti-ORF8 and anti-N-CTD IgG ELISA assays using receiver-operating-characteristic (ROC) curves. The sensitivity of the anti-ORF8 and anti-N-CTD ELISA for detecting past infection was 83.2% and 99.3%, respectively. Specificity of anti-ORF8 ELISA was 96.8 % vs. the pre-pandemic cohort or 93% considering the pre-pandemic and vaccine cohorts together. The anti-N-CTD ELISA specificity of 98.9% in the pre-pandemic cohort, 93% in BNT vaccinated and only 4 % in CoronaVac vaccinated cohorts. Anti-N-CTD antibody was longer-lived than anti-ORF8 antibody after natural infection | ||
| 520 | |a CONCLUSIONS: Anti-N-CTD antibody assays provide good discrimination between natural infection and vaccination in BNT162b2 vaccinated individuals. Anti-ORF8 antibody can help discriminate infection from vaccination in either type of vaccine and help estimate infection attack rates (IAR) in communities | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a N-CTD | |
| 650 | 4 | |a Natural infection | |
| 650 | 4 | |a ORF8 | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a Vaccine induced immunity | |
| 650 | 4 | |a antibody | |
| 650 | 7 | |a BNT162 Vaccine |2 NLM | |
| 650 | 7 | |a Viral Vaccines |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 700 | 1 | |a Lau, Jonathan J |e verfasserin |4 aut | |
| 700 | 1 | |a Tsang, Leo C H |e verfasserin |4 aut | |
| 700 | 1 | |a Leung, Kathy |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Cheuk Kwong |e verfasserin |4 aut | |
| 700 | 1 | |a Hachim, Asmaa |e verfasserin |4 aut | |
| 700 | 1 | |a Kavian, Niloufar |e verfasserin |4 aut | |
| 700 | 1 | |a Chaothai, Sara |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, Ricky W K |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jennifer K M |e verfasserin |4 aut | |
| 700 | 1 | |a Chai, Zacary Y H |e verfasserin |4 aut | |
| 700 | 1 | |a Mori, Masashi |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Chao |e verfasserin |4 aut | |
| 700 | 1 | |a Yiu, Karen |e verfasserin |4 aut | |
| 700 | 1 | |a Hui, David S C |e verfasserin |4 aut | |
| 700 | 1 | |a Amarasinghe, Gaya K |e verfasserin |4 aut | |
| 700 | 1 | |a Poon, Leo L M |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Joseph T |e verfasserin |4 aut | |
| 700 | 1 | |a Valkenburg, Sophie A |e verfasserin |4 aut | |
| 700 | 1 | |a Peiris, Malik |e verfasserin |4 aut | |
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