Convalescent plasma donors show enhanced cross-reactive neutralizing antibody response to antigenic variants of SARS-CoV-2 following immunization

Heli Harvala; Dung Nguyen; Peter Simmonds; Abigail A. Lamikanra; Hoi Pat Tsang; Ashley Otter; Piet Maes; Mhairi Webster; Adam Clarkson; Fotini Kaloyirou; Valerie Hopkins; Stephen M. Laidlaw; Miles Carroll; Ana Mora; Alexandra Griffiths; Sheila MacLennan; Lise Estcourt; David J. Roberts

doi:10.1111/trf.16934

Convalescent plasma donors show enhanced cross-reactive neutralizing antibody response to antigenic variants of SARS-CoV-2 following immunization

Heli Harvala^*, Dung Nguyen, Peter Simmonds, Abigail A. Lamikanra, Hoi Pat Tsang, Ashley Otter, Piet Maes, Mhairi Webster, Adam Clarkson, Fotini Kaloyirou, Valerie Hopkins, Stephen M. Laidlaw, Miles Carroll, Ana Mora, Alexandra Griffiths, Sheila MacLennan, Lise Estcourt, David J. Roberts

^*Corresponding author for this work

UK Health Security Agency

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

14 Downloads (Pure)

Abstract

Background: The therapeutic benefit of convalescent plasma (CP) therapy to treat COVID-19 may derive from neutralizing antibodies (nAbs) to SARS-CoV-2. To investigate the effects of antigenic variation on neutralization potency of CP, we compared nAb titers against prototype and recently emerging strains of SARS-CoV-2, including Delta and Omicron, in CP donors previously infected with SARS-CoV-2 before and after immunization.

Methods and Materials: Samples were assayed from previously SARS-CoV-2 infected donors before (n = 17) and after one (n = 43) or two (n = 71) doses of Astra-Zeneca or Pfizer vaccinations. Ab titers against Wuhan/wild type (WT), Alpha, Beta, and Delta SARS-CoV-2 strains were determined by live virus microneutralization assay while titers to Omicron used a focus reduction neutralization test. Anti-spike antibody was assayed by Elecsys anti-SARS-CoV-2 quantitative spike assay (Roche).

Results: Unvaccinated donors showed a geometric mean titer (GMT) of 148 against WT, 80 against Alpha but mostly failed to neutralize Beta, Delta, and Omicron strains. Contrastingly, high GMTs were observed in vaccinated donors against all SARS-CoV-2 strains after one vaccine dose (WT:703; Alpha:692; Beta:187; Delta:215; Omicron:434). By ROC analysis, reactivity in the Roche quantitative Elecsys spike assay of 20,000 U/mL was highly predictive of donations with nAb titers of ≥1:640 against Delta (90% sensitivity; 97% specificity) and ≥1:320 against Omicron (89% sensitivity; 81% specificity).

Discussion: Vaccination of previously infected CP donors induced high levels of broadly neutralizing antibodies against circulating antigenic variants of SARS-CoV-2. High titer donations could be reliably identified by automated quantitative anti-spike antibody assay, enabling large-scale preselection of high-titer convalescent plasma.

Original language	English
Pages (from-to)	1347-1354
Number of pages	8
Journal	Transfusion
Volume	62
Issue number	7
Early online date	2 Jun 2022
DOIs	https://doi.org/10.1111/trf.16934
Publication status	Published - 11 Jul 2022

Bibliographical note

Funding Information: The study was funded by the European Commission (HORIZON2020 project Support‐E, no. 101015756) to HH, LE, and DJR. LE and DJR were also supported by the NIHR plasma grant (RECPLAS) and NHS Blood and Transplant R&D funding. DN and SL were supported by the Oak Foundation grant of MC.

Open Access: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Publisher Copyright: © 2022 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.

Citation: Harvala, H, Nguyen, D, Simmonds, P, Lamikanra, AA, Tsang, HP, Otter, A, et al. Convalescent plasma donors show enhanced cross-reactive neutralizing antibody response to antigenic variants of SARS-CoV-2 following immunization. Transfusion. 2022; 62( 7): 1347– 1354.

DOI: https://doi.org/10.1111/trf.16934

Keywords

COVID-19
Delta
Omicron
SARS-CoV-2
antibody neutralization
antigenic variants
convalescent plasma
vaccination

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1111/trf.16934Licence: CC BY

Harvala2022ConvalescentPlasmaDonorsShowEnhancedCross-ReactiveNeutralizingAntibodyResponseTransfusionFinal published version, 1.24 MBLicence: CC BY

Cite this

Harvala, H., Nguyen, D., Simmonds, P., Lamikanra, A. A., Tsang, H. P., Otter, A., Maes, P., Webster, M., Clarkson, A., Kaloyirou, F., Hopkins, V., Laidlaw, S. M., Carroll, M., Mora, A., Griffiths, A., MacLennan, S., Estcourt, L., & Roberts, D. J. (2022). Convalescent plasma donors show enhanced cross-reactive neutralizing antibody response to antigenic variants of SARS-CoV-2 following immunization. Transfusion, 62(7), 1347-1354. https://doi.org/10.1111/trf.16934

@article{be38bf42d20940d9a2c01102af9694fd,

title = "Convalescent plasma donors show enhanced cross-reactive neutralizing antibody response to antigenic variants of SARS-CoV-2 following immunization",

abstract = "Background: The therapeutic benefit of convalescent plasma (CP) therapy to treat COVID-19 may derive from neutralizing antibodies (nAbs) to SARS-CoV-2. To investigate the effects of antigenic variation on neutralization potency of CP, we compared nAb titers against prototype and recently emerging strains of SARS-CoV-2, including Delta and Omicron, in CP donors previously infected with SARS-CoV-2 before and after immunization. Methods and Materials: Samples were assayed from previously SARS-CoV-2 infected donors before (n = 17) and after one (n = 43) or two (n = 71) doses of Astra-Zeneca or Pfizer vaccinations. Ab titers against Wuhan/wild type (WT), Alpha, Beta, and Delta SARS-CoV-2 strains were determined by live virus microneutralization assay while titers to Omicron used a focus reduction neutralization test. Anti-spike antibody was assayed by Elecsys anti-SARS-CoV-2 quantitative spike assay (Roche). Results: Unvaccinated donors showed a geometric mean titer (GMT) of 148 against WT, 80 against Alpha but mostly failed to neutralize Beta, Delta, and Omicron strains. Contrastingly, high GMTs were observed in vaccinated donors against all SARS-CoV-2 strains after one vaccine dose (WT:703; Alpha:692; Beta:187; Delta:215; Omicron:434). By ROC analysis, reactivity in the Roche quantitative Elecsys spike assay of 20,000 U/mL was highly predictive of donations with nAb titers of ≥1:640 against Delta (90% sensitivity; 97% specificity) and ≥1:320 against Omicron (89% sensitivity; 81% specificity). Discussion: Vaccination of previously infected CP donors induced high levels of broadly neutralizing antibodies against circulating antigenic variants of SARS-CoV-2. High titer donations could be reliably identified by automated quantitative anti-spike antibody assay, enabling large-scale preselection of high-titer convalescent plasma.",

keywords = "COVID-19, Delta, Omicron, SARS-CoV-2, antibody neutralization, antigenic variants, convalescent plasma, vaccination",

author = "Heli Harvala and Dung Nguyen and Peter Simmonds and Lamikanra, {Abigail A.} and Tsang, {Hoi Pat} and Ashley Otter and Piet Maes and Mhairi Webster and Adam Clarkson and Fotini Kaloyirou and Valerie Hopkins and Laidlaw, {Stephen M.} and Miles Carroll and Ana Mora and Alexandra Griffiths and Sheila MacLennan and Lise Estcourt and Roberts, {David J.}",

note = "Funding Information: The study was funded by the European Commission (HORIZON2020 project Support‐E, no. 101015756) to HH, LE, and DJR. LE and DJR were also supported by the NIHR plasma grant (RECPLAS) and NHS Blood and Transplant R&D funding. DN and SL were supported by the Oak Foundation grant of MC. Open Access: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Publisher Copyright: {\textcopyright} 2022 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB. Citation: Harvala, H, Nguyen, D, Simmonds, P, Lamikanra, AA, Tsang, HP, Otter, A, et al. Convalescent plasma donors show enhanced cross-reactive neutralizing antibody response to antigenic variants of SARS-CoV-2 following immunization. Transfusion. 2022; 62( 7): 1347– 1354. DOI: https://doi.org/10.1111/trf.16934",

year = "2022",

month = jul,

day = "11",

doi = "10.1111/trf.16934",

language = "English",

volume = "62",

pages = "1347--1354",

journal = "Transfusion",

issn = "0041-1132",

publisher = "wiley",

number = "7",

}

Harvala, H, Nguyen, D, Simmonds, P, Lamikanra, AA, Tsang, HP, Otter, A, Maes, P, Webster, M, Clarkson, A, Kaloyirou, F, Hopkins, V, Laidlaw, SM, Carroll, M, Mora, A, Griffiths, A, MacLennan, S, Estcourt, L & Roberts, DJ 2022, 'Convalescent plasma donors show enhanced cross-reactive neutralizing antibody response to antigenic variants of SARS-CoV-2 following immunization', Transfusion, vol. 62, no. 7, pp. 1347-1354. https://doi.org/10.1111/trf.16934

TY - JOUR

T1 - Convalescent plasma donors show enhanced cross-reactive neutralizing antibody response to antigenic variants of SARS-CoV-2 following immunization

AU - Harvala, Heli

AU - Nguyen, Dung

AU - Simmonds, Peter

AU - Lamikanra, Abigail A.

AU - Tsang, Hoi Pat

AU - Otter, Ashley

AU - Maes, Piet

AU - Webster, Mhairi

AU - Clarkson, Adam

AU - Kaloyirou, Fotini

AU - Hopkins, Valerie

AU - Laidlaw, Stephen M.

AU - Carroll, Miles

AU - Mora, Ana

AU - Griffiths, Alexandra

AU - MacLennan, Sheila

AU - Estcourt, Lise

AU - Roberts, David J.

N1 - Funding Information: The study was funded by the European Commission (HORIZON2020 project Support‐E, no. 101015756) to HH, LE, and DJR. LE and DJR were also supported by the NIHR plasma grant (RECPLAS) and NHS Blood and Transplant R&D funding. DN and SL were supported by the Oak Foundation grant of MC. Open Access: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Publisher Copyright: © 2022 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB. Citation: Harvala, H, Nguyen, D, Simmonds, P, Lamikanra, AA, Tsang, HP, Otter, A, et al. Convalescent plasma donors show enhanced cross-reactive neutralizing antibody response to antigenic variants of SARS-CoV-2 following immunization. Transfusion. 2022; 62( 7): 1347– 1354. DOI: https://doi.org/10.1111/trf.16934

PY - 2022/7/11

Y1 - 2022/7/11

N2 - Background: The therapeutic benefit of convalescent plasma (CP) therapy to treat COVID-19 may derive from neutralizing antibodies (nAbs) to SARS-CoV-2. To investigate the effects of antigenic variation on neutralization potency of CP, we compared nAb titers against prototype and recently emerging strains of SARS-CoV-2, including Delta and Omicron, in CP donors previously infected with SARS-CoV-2 before and after immunization. Methods and Materials: Samples were assayed from previously SARS-CoV-2 infected donors before (n = 17) and after one (n = 43) or two (n = 71) doses of Astra-Zeneca or Pfizer vaccinations. Ab titers against Wuhan/wild type (WT), Alpha, Beta, and Delta SARS-CoV-2 strains were determined by live virus microneutralization assay while titers to Omicron used a focus reduction neutralization test. Anti-spike antibody was assayed by Elecsys anti-SARS-CoV-2 quantitative spike assay (Roche). Results: Unvaccinated donors showed a geometric mean titer (GMT) of 148 against WT, 80 against Alpha but mostly failed to neutralize Beta, Delta, and Omicron strains. Contrastingly, high GMTs were observed in vaccinated donors against all SARS-CoV-2 strains after one vaccine dose (WT:703; Alpha:692; Beta:187; Delta:215; Omicron:434). By ROC analysis, reactivity in the Roche quantitative Elecsys spike assay of 20,000 U/mL was highly predictive of donations with nAb titers of ≥1:640 against Delta (90% sensitivity; 97% specificity) and ≥1:320 against Omicron (89% sensitivity; 81% specificity). Discussion: Vaccination of previously infected CP donors induced high levels of broadly neutralizing antibodies against circulating antigenic variants of SARS-CoV-2. High titer donations could be reliably identified by automated quantitative anti-spike antibody assay, enabling large-scale preselection of high-titer convalescent plasma.

AB - Background: The therapeutic benefit of convalescent plasma (CP) therapy to treat COVID-19 may derive from neutralizing antibodies (nAbs) to SARS-CoV-2. To investigate the effects of antigenic variation on neutralization potency of CP, we compared nAb titers against prototype and recently emerging strains of SARS-CoV-2, including Delta and Omicron, in CP donors previously infected with SARS-CoV-2 before and after immunization. Methods and Materials: Samples were assayed from previously SARS-CoV-2 infected donors before (n = 17) and after one (n = 43) or two (n = 71) doses of Astra-Zeneca or Pfizer vaccinations. Ab titers against Wuhan/wild type (WT), Alpha, Beta, and Delta SARS-CoV-2 strains were determined by live virus microneutralization assay while titers to Omicron used a focus reduction neutralization test. Anti-spike antibody was assayed by Elecsys anti-SARS-CoV-2 quantitative spike assay (Roche). Results: Unvaccinated donors showed a geometric mean titer (GMT) of 148 against WT, 80 against Alpha but mostly failed to neutralize Beta, Delta, and Omicron strains. Contrastingly, high GMTs were observed in vaccinated donors against all SARS-CoV-2 strains after one vaccine dose (WT:703; Alpha:692; Beta:187; Delta:215; Omicron:434). By ROC analysis, reactivity in the Roche quantitative Elecsys spike assay of 20,000 U/mL was highly predictive of donations with nAb titers of ≥1:640 against Delta (90% sensitivity; 97% specificity) and ≥1:320 against Omicron (89% sensitivity; 81% specificity). Discussion: Vaccination of previously infected CP donors induced high levels of broadly neutralizing antibodies against circulating antigenic variants of SARS-CoV-2. High titer donations could be reliably identified by automated quantitative anti-spike antibody assay, enabling large-scale preselection of high-titer convalescent plasma.

KW - COVID-19

KW - Delta

KW - Omicron

KW - SARS-CoV-2

KW - antibody neutralization

KW - antigenic variants

KW - convalescent plasma

KW - vaccination

UR - http://www.scopus.com/inward/record.url?scp=85131100484&partnerID=8YFLogxK

U2 - 10.1111/trf.16934

DO - 10.1111/trf.16934

M3 - Article

C2 - 35588314

AN - SCOPUS:85131100484

SN - 0041-1132

VL - 62

SP - 1347

EP - 1354

JO - Transfusion

JF - Transfusion

IS - 7

ER -

Convalescent plasma donors show enhanced cross-reactive neutralizing antibody response to antigenic variants of SARS-CoV-2 following immunization

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this