Correlation of the Commercial Anti-SARS-CoV-2 Receptor Binding Domain Antibody Test with the Chemiluminescent Reduction Neutralizing Test and Possible Detection of Antibodies to Emerging Variants

ABSTRACT Serological tests are beneficial for recognizing the immune response against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). To identify protective immunity, optimization of the chemiluminescent reduction neutralizing test (CRNT) is critical. Whether commercial antibody tests...

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Main Authors: Yoshitomo Morinaga, Hideki Tani, Yasushi Terasaki, Satoshi Nomura, Hitoshi Kawasuji, Takahisa Shimada, Emiko Igarashi, Yumiko Saga, Yoshihiro Yoshida, Rei Yasukochi, Makito Kaneda, Yushi Murai, Akitoshi Ueno, Yuki Miyajima, Yasutaka Fukui, Kentaro Nagaoka, Chikako Ono, Yoshiharu Matsuura, Takashi Fujimura, Yoichi Ishida, Kazunori Oishi, Yoshihiro Yamamoto
Format: Article
Language:English
Published: American Society for Microbiology 2021-12-01
Series:Microbiology Spectrum
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/Spectrum.00560-21
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author Yoshitomo Morinaga
Hideki Tani
Yasushi Terasaki
Satoshi Nomura
Hitoshi Kawasuji
Takahisa Shimada
Emiko Igarashi
Yumiko Saga
Yoshihiro Yoshida
Rei Yasukochi
Makito Kaneda
Yushi Murai
Akitoshi Ueno
Yuki Miyajima
Yasutaka Fukui
Kentaro Nagaoka
Chikako Ono
Yoshiharu Matsuura
Takashi Fujimura
Yoichi Ishida
Kazunori Oishi
Yoshihiro Yamamoto
author_facet Yoshitomo Morinaga
Hideki Tani
Yasushi Terasaki
Satoshi Nomura
Hitoshi Kawasuji
Takahisa Shimada
Emiko Igarashi
Yumiko Saga
Yoshihiro Yoshida
Rei Yasukochi
Makito Kaneda
Yushi Murai
Akitoshi Ueno
Yuki Miyajima
Yasutaka Fukui
Kentaro Nagaoka
Chikako Ono
Yoshiharu Matsuura
Takashi Fujimura
Yoichi Ishida
Kazunori Oishi
Yoshihiro Yamamoto
author_sort Yoshitomo Morinaga
collection DOAJ
description ABSTRACT Serological tests are beneficial for recognizing the immune response against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). To identify protective immunity, optimization of the chemiluminescent reduction neutralizing test (CRNT) is critical. Whether commercial antibody tests have comparable accuracy is unknown. Serum samples were obtained from COVID-19 patients (n = 74), SARS-CoV-2 PCR-negative (n = 179), and suspected healthy individuals (n = 229) before SARS-CoV-2 variants had been detected locally. The convalescent phase was defined as the period after day 10 from disease onset or the episode of close contact. The CRNT using pseudotyped viruses displaying the wild-type (WT) spike protein and a commercial anti-receptor-binding domain (RBD) antibody test were assayed. Serology for the B.1.1.7 and B.1.351 variants was also assayed. Both tests concurred for symptomatic COVID-19 patients in the convalescent phase. They clearly differentiated between patients and suspected healthy individuals (sensitivity: 95.8% and 100%, respectively; specificity: 99.1% and 100%, respectively). Anti-RBD antibody test results correlated with neutralizing titers (r = 0.31, 95% confidence interval [CI] 0.22–0.38). Compared with the WT, lower CRNT values were observed for the variants. Of the samples with ≥100 U/mL by the anti-RBD antibody test, 77.8% and 88.9% showed ≥50% neutralization against the B.1.1.7 and the B.1.351 variants, respectively. Exceeding 100 U/mL in the anti-RBD antibody test was associated with neutralization of variants (P < 0.01). The CRNT and commercial anti-RBD antibody test effectively classified convalescent COVID-19 patients. Strong positive results with the anti-RBD antibody test can reflect neutralizing activity against emerging variants. IMPORTANCE This study provides a diagnostic evidence of test validity, which can lead to vaccine efficacy and proof of recovery after COVID-19. It is not easy to know neutralization against SARS-CoV-2 in the clinical laboratory because of technical and biohazard issues. The correlation of the quantitative anti-receptor-binding domain antibody test, which is widely available, with neutralizing test indicates that we can know indirectly the state of acquisition of functional immunity against wild and variant-type viruses in the clinical laboratory.
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spelling doaj.art-a628250de1dd4f819d6c39bc77c949ba2022-12-22T04:15:51ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972021-12-019310.1128/Spectrum.00560-21Correlation of the Commercial Anti-SARS-CoV-2 Receptor Binding Domain Antibody Test with the Chemiluminescent Reduction Neutralizing Test and Possible Detection of Antibodies to Emerging VariantsYoshitomo Morinaga0Hideki Tani1Yasushi Terasaki2Satoshi Nomura3Hitoshi Kawasuji4Takahisa Shimada5Emiko Igarashi6Yumiko Saga7Yoshihiro Yoshida8Rei Yasukochi9Makito Kaneda10Yushi Murai11Akitoshi Ueno12Yuki Miyajima13Yasutaka Fukui14Kentaro Nagaoka15Chikako Ono16Yoshiharu Matsuura17Takashi Fujimura18Yoichi Ishida19Kazunori Oishi20Yoshihiro Yamamoto21Department of Microbiology, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanDepartment of Microbiology, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanToyama City Hospital, Toyama, JapanToyama City Hospital, Toyama, JapanDepartment of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanDepartment of Microbiology, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanDepartment of Virology, Toyama Institute of Health, Toyama, JapanDepartment of Microbiology, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanDepartment of Microbiology, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanDepartment of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanDepartment of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanDepartment of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanDepartment of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanDepartment of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanDepartment of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanDepartment of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanLaboratory of Virus Control, Center for Infectious Disease Education and Research (CiDER), Osaka University, Osaka, JapanLaboratory of Virus Control, Center for Infectious Disease Education and Research (CiDER), Osaka University, Osaka, JapanToyama City Hospital, Toyama, JapanToyama City Hospital, Toyama, JapanToyama Institute of Health, Toyama, JapanDepartment of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, JapanABSTRACT Serological tests are beneficial for recognizing the immune response against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). To identify protective immunity, optimization of the chemiluminescent reduction neutralizing test (CRNT) is critical. Whether commercial antibody tests have comparable accuracy is unknown. Serum samples were obtained from COVID-19 patients (n = 74), SARS-CoV-2 PCR-negative (n = 179), and suspected healthy individuals (n = 229) before SARS-CoV-2 variants had been detected locally. The convalescent phase was defined as the period after day 10 from disease onset or the episode of close contact. The CRNT using pseudotyped viruses displaying the wild-type (WT) spike protein and a commercial anti-receptor-binding domain (RBD) antibody test were assayed. Serology for the B.1.1.7 and B.1.351 variants was also assayed. Both tests concurred for symptomatic COVID-19 patients in the convalescent phase. They clearly differentiated between patients and suspected healthy individuals (sensitivity: 95.8% and 100%, respectively; specificity: 99.1% and 100%, respectively). Anti-RBD antibody test results correlated with neutralizing titers (r = 0.31, 95% confidence interval [CI] 0.22–0.38). Compared with the WT, lower CRNT values were observed for the variants. Of the samples with ≥100 U/mL by the anti-RBD antibody test, 77.8% and 88.9% showed ≥50% neutralization against the B.1.1.7 and the B.1.351 variants, respectively. Exceeding 100 U/mL in the anti-RBD antibody test was associated with neutralization of variants (P < 0.01). The CRNT and commercial anti-RBD antibody test effectively classified convalescent COVID-19 patients. Strong positive results with the anti-RBD antibody test can reflect neutralizing activity against emerging variants. IMPORTANCE This study provides a diagnostic evidence of test validity, which can lead to vaccine efficacy and proof of recovery after COVID-19. It is not easy to know neutralization against SARS-CoV-2 in the clinical laboratory because of technical and biohazard issues. The correlation of the quantitative anti-receptor-binding domain antibody test, which is widely available, with neutralizing test indicates that we can know indirectly the state of acquisition of functional immunity against wild and variant-type viruses in the clinical laboratory.https://journals.asm.org/doi/10.1128/Spectrum.00560-21neutralizing antibodiesseroconversionreceptor-binding domainconvalescenthigh throughput
spellingShingle Yoshitomo Morinaga
Hideki Tani
Yasushi Terasaki
Satoshi Nomura
Hitoshi Kawasuji
Takahisa Shimada
Emiko Igarashi
Yumiko Saga
Yoshihiro Yoshida
Rei Yasukochi
Makito Kaneda
Yushi Murai
Akitoshi Ueno
Yuki Miyajima
Yasutaka Fukui
Kentaro Nagaoka
Chikako Ono
Yoshiharu Matsuura
Takashi Fujimura
Yoichi Ishida
Kazunori Oishi
Yoshihiro Yamamoto
Correlation of the Commercial Anti-SARS-CoV-2 Receptor Binding Domain Antibody Test with the Chemiluminescent Reduction Neutralizing Test and Possible Detection of Antibodies to Emerging Variants
Microbiology Spectrum
neutralizing antibodies
seroconversion
receptor-binding domain
convalescent
high throughput
title Correlation of the Commercial Anti-SARS-CoV-2 Receptor Binding Domain Antibody Test with the Chemiluminescent Reduction Neutralizing Test and Possible Detection of Antibodies to Emerging Variants
title_full Correlation of the Commercial Anti-SARS-CoV-2 Receptor Binding Domain Antibody Test with the Chemiluminescent Reduction Neutralizing Test and Possible Detection of Antibodies to Emerging Variants
title_fullStr Correlation of the Commercial Anti-SARS-CoV-2 Receptor Binding Domain Antibody Test with the Chemiluminescent Reduction Neutralizing Test and Possible Detection of Antibodies to Emerging Variants
title_full_unstemmed Correlation of the Commercial Anti-SARS-CoV-2 Receptor Binding Domain Antibody Test with the Chemiluminescent Reduction Neutralizing Test and Possible Detection of Antibodies to Emerging Variants
title_short Correlation of the Commercial Anti-SARS-CoV-2 Receptor Binding Domain Antibody Test with the Chemiluminescent Reduction Neutralizing Test and Possible Detection of Antibodies to Emerging Variants
title_sort correlation of the commercial anti sars cov 2 receptor binding domain antibody test with the chemiluminescent reduction neutralizing test and possible detection of antibodies to emerging variants
topic neutralizing antibodies
seroconversion
receptor-binding domain
convalescent
high throughput
url https://journals.asm.org/doi/10.1128/Spectrum.00560-21
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