Correlation of SARS-CoV-2 Viral Neutralizing Antibody Titers with Anti-Spike Antibodies and ACE-2 Inhibition among Vaccinated Individuals

ABSTRACT SARS-CoV-2 anti-spike antibody concentrations and angiotensin converting enzyme-2 (ACE-2) inhibition have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. We tested the correlation of these measures among vaccinat...

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Main Authors: Brian Grunau, Martin Prusinkiewicz, Michael Asamoah-Boaheng, Liam Golding, Pascal M. Lavoie, Martin Petric, Paul N. Levett, Scott Haig, Vilte Barakauskas, Mohammad Ehsanul Karim, Agatha N. Jassem, Steven J. Drews, Sadaf Sediqi, David M. Goldfarb
Format: Article
Language:English
Published: American Society for Microbiology 2022-10-01
Series:Microbiology Spectrum
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/spectrum.01315-22
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author Brian Grunau
Martin Prusinkiewicz
Michael Asamoah-Boaheng
Liam Golding
Pascal M. Lavoie
Martin Petric
Paul N. Levett
Scott Haig
Vilte Barakauskas
Mohammad Ehsanul Karim
Agatha N. Jassem
Steven J. Drews
Sadaf Sediqi
David M. Goldfarb
author_facet Brian Grunau
Martin Prusinkiewicz
Michael Asamoah-Boaheng
Liam Golding
Pascal M. Lavoie
Martin Petric
Paul N. Levett
Scott Haig
Vilte Barakauskas
Mohammad Ehsanul Karim
Agatha N. Jassem
Steven J. Drews
Sadaf Sediqi
David M. Goldfarb
author_sort Brian Grunau
collection DOAJ
description ABSTRACT SARS-CoV-2 anti-spike antibody concentrations and angiotensin converting enzyme-2 (ACE-2) inhibition have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. We tested the correlation of these measures among vaccinated participants, and examined subgroups based on duration since vaccination and vaccine dosing intervals. We analyzed 120 samples from two-dose mRNA vaccinees without previous COVID-19. We calculated Spearman correlation coefficients between wild-type viral neutralizing antibody titers and: anti-spike (total and IgG), anti-receptor-binding-domain (RBD), and anti-N-terminal-domain (NTD) antibodies; and ACE-2 binding by RBD. We performed three secondary analyses, dichotomizing samples by the first vaccination-to-blood collection interval, second vaccination-to-blood collection interval, and by the vaccine dosing interval (all groups divided by the median), and compared correlation coefficients (Fisher’s Z test). Of 120 participants, 63 (53%) were women, 91 (76%) and 29 (24%) received BNT162b2 and mRNA-1273 vaccines, respectively. Overall, live viral neutralization was correlated with anti-spike total antibody (correlation coefficient = 0.80), anti-spike IgG (0.63), anti-RBD IgG (0.62), anti-NTD IgG (0.64), and RBD ACE2 binding (0.65). Samples with long (>158 days) first vaccination-to-blood collection and long (>71 days) second vaccination-to-blood collection intervals demonstrated higher correlation coefficients, compared with short groups. When comparing cases divided by short (≤39 days) versus long vaccine dosing intervals, only correlation with RBD-ACE-2 binding inhibition was higher in the long group. Among COVID-negative mRNA vaccinees, anti-spike antibody and ACE-2 inhibition concentrations are correlated with live viral neutralizing antibody titers. Correlation was stronger among samples collected at later durations from vaccination. IMPORTANCE Live viral neutralizing antibody titers are an accepted measure of immunity; however, testing procedures are labor-intensive. COVID-19 antibody and angiotensin converting enzyme-2 (ACE-2) levels have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. Using samples from 120 two-dose mRNA vaccinees without previous COVID-19, we found that live viral neutralization was correlated with COVID-19 antibody and ACE2 binding levels. When grouping samples by the time interval between vaccination and sample blood collection, samples collected over 158 days after the first vaccine and over 71 days from the second vaccine demonstrated stronger correlation between live viral neutralization titers and both antibody and ACE2 levels, in comparison to those collected earlier.
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spelling doaj.art-4fcdf3188a27408e85a2248536bfdc7b2022-12-22T02:40:54ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-10-0110510.1128/spectrum.01315-22Correlation of SARS-CoV-2 Viral Neutralizing Antibody Titers with Anti-Spike Antibodies and ACE-2 Inhibition among Vaccinated IndividualsBrian Grunau0Martin Prusinkiewicz1Michael Asamoah-Boaheng2Liam Golding3Pascal M. Lavoie4Martin Petric5Paul N. Levett6Scott Haig7Vilte Barakauskas8Mohammad Ehsanul Karim9Agatha N. Jassem10Steven J. Drews11Sadaf Sediqi12David M. Goldfarb13Centre for Health Evaluation & Outcome Sciences, St. Paul’s Hospital, Vancouver, British Columbia, CanadaDepartment of Pediatrics, University of British Columbia, Vancouver, British Columbia, CanadaCentre for Health Evaluation & Outcome Sciences, St. Paul’s Hospital, Vancouver, British Columbia, CanadaDepartment of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, CanadaDepartment of Pediatrics, University of British Columbia, Vancouver, British Columbia, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, CanadaBritish Columbia Emergency Health Services, Vancouver, British Columbia, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, CanadaCentre for Health Evaluation & Outcome Sciences, St. Paul’s Hospital, Vancouver, British Columbia, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, CanadaCanadian Blood Services, Ottawa, Ontario, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, CanadaABSTRACT SARS-CoV-2 anti-spike antibody concentrations and angiotensin converting enzyme-2 (ACE-2) inhibition have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. We tested the correlation of these measures among vaccinated participants, and examined subgroups based on duration since vaccination and vaccine dosing intervals. We analyzed 120 samples from two-dose mRNA vaccinees without previous COVID-19. We calculated Spearman correlation coefficients between wild-type viral neutralizing antibody titers and: anti-spike (total and IgG), anti-receptor-binding-domain (RBD), and anti-N-terminal-domain (NTD) antibodies; and ACE-2 binding by RBD. We performed three secondary analyses, dichotomizing samples by the first vaccination-to-blood collection interval, second vaccination-to-blood collection interval, and by the vaccine dosing interval (all groups divided by the median), and compared correlation coefficients (Fisher’s Z test). Of 120 participants, 63 (53%) were women, 91 (76%) and 29 (24%) received BNT162b2 and mRNA-1273 vaccines, respectively. Overall, live viral neutralization was correlated with anti-spike total antibody (correlation coefficient = 0.80), anti-spike IgG (0.63), anti-RBD IgG (0.62), anti-NTD IgG (0.64), and RBD ACE2 binding (0.65). Samples with long (>158 days) first vaccination-to-blood collection and long (>71 days) second vaccination-to-blood collection intervals demonstrated higher correlation coefficients, compared with short groups. When comparing cases divided by short (≤39 days) versus long vaccine dosing intervals, only correlation with RBD-ACE-2 binding inhibition was higher in the long group. Among COVID-negative mRNA vaccinees, anti-spike antibody and ACE-2 inhibition concentrations are correlated with live viral neutralizing antibody titers. Correlation was stronger among samples collected at later durations from vaccination. IMPORTANCE Live viral neutralizing antibody titers are an accepted measure of immunity; however, testing procedures are labor-intensive. COVID-19 antibody and angiotensin converting enzyme-2 (ACE-2) levels have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. Using samples from 120 two-dose mRNA vaccinees without previous COVID-19, we found that live viral neutralization was correlated with COVID-19 antibody and ACE2 binding levels. When grouping samples by the time interval between vaccination and sample blood collection, samples collected over 158 days after the first vaccine and over 71 days from the second vaccine demonstrated stronger correlation between live viral neutralization titers and both antibody and ACE2 levels, in comparison to those collected earlier.https://journals.asm.org/doi/10.1128/spectrum.01315-22neutralizing antibodiesSARS-CoV-2COVID-19anti-spikeACE-2
spellingShingle Brian Grunau
Martin Prusinkiewicz
Michael Asamoah-Boaheng
Liam Golding
Pascal M. Lavoie
Martin Petric
Paul N. Levett
Scott Haig
Vilte Barakauskas
Mohammad Ehsanul Karim
Agatha N. Jassem
Steven J. Drews
Sadaf Sediqi
David M. Goldfarb
Correlation of SARS-CoV-2 Viral Neutralizing Antibody Titers with Anti-Spike Antibodies and ACE-2 Inhibition among Vaccinated Individuals
Microbiology Spectrum
neutralizing antibodies
SARS-CoV-2
COVID-19
anti-spike
ACE-2
title Correlation of SARS-CoV-2 Viral Neutralizing Antibody Titers with Anti-Spike Antibodies and ACE-2 Inhibition among Vaccinated Individuals
title_full Correlation of SARS-CoV-2 Viral Neutralizing Antibody Titers with Anti-Spike Antibodies and ACE-2 Inhibition among Vaccinated Individuals
title_fullStr Correlation of SARS-CoV-2 Viral Neutralizing Antibody Titers with Anti-Spike Antibodies and ACE-2 Inhibition among Vaccinated Individuals
title_full_unstemmed Correlation of SARS-CoV-2 Viral Neutralizing Antibody Titers with Anti-Spike Antibodies and ACE-2 Inhibition among Vaccinated Individuals
title_short Correlation of SARS-CoV-2 Viral Neutralizing Antibody Titers with Anti-Spike Antibodies and ACE-2 Inhibition among Vaccinated Individuals
title_sort correlation of sars cov 2 viral neutralizing antibody titers with anti spike antibodies and ace 2 inhibition among vaccinated individuals
topic neutralizing antibodies
SARS-CoV-2
COVID-19
anti-spike
ACE-2
url https://journals.asm.org/doi/10.1128/spectrum.01315-22
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