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. 2022 Apr 14:12:822599.
doi: 10.3389/fcimb.2022.822599. eCollection 2022.

Estimating the Neutralizing Effect and Titer Correlation of Semi-Quantitative Anti-SARS-CoV-2 Antibody Immunoassays

Beomki Lee  1 , Jae-Hoon Ko  2 , Jiho Park  3 , Hee-Won Moon  4 , Jin Yang Baek  5 , Sunhee Jung  6 , Hee-Young Lim  6 , Kyung-Chang Kim  6 , Kyungmin Huh  2 , Sun Young Cho  2 , Cheol-In Kang  2 , Doo Ryeon Chung  2 , Hee Jae Huh  1 , Chi Ryang Chung  7 , Yae-Jean Kim  8 , Eun-Jeong Joo  9 , Eun-Suk Kang  1 , Kyong Ran Peck  2
Affiliations

Estimating the Neutralizing Effect and Titer Correlation of Semi-Quantitative Anti-SARS-CoV-2 Antibody Immunoassays

Beomki Lee et al. Front Cell Infect Microbiol. .

Abstract

For the clinical application of semi-quantitative anti-SARS-CoV-2 antibody tests, the analytical performance and titer correlation of the plaque reduction neutralization test (PRNT) need to be investigated. We evaluated the analytical performance and PRNT titer-correlation of one surrogate virus neutralization test (sVNT) kit and three chemiluminescent assays. We measured the total antibodies for the receptor-binding domain (RBD) of the spike protein, total antibodies for the nucleocapsid protein (NP), and IgG antibodies for the RBD. All three chemiluminescent assays showed high analytical performance for the detection of SARS-CoV-2 infection, with a sensitivity ≥ 98% and specificity ≥ 99%; those of the sVNT were slightly lower. The representativeness of the neutralizing activity of PRNT ND50 ≥ 20 was comparable among the four immunoassays (Cohen's kappa ≈ 0.80). Quantitative titer correlation for high PRNT titers of ND50 ≥ 50, 200, and 1,000 was investigated with new cut-off values; the anti-RBD IgG antibody kit showed the best performance. It also showed the best linear correlation with PRNT titer in both the acute and convalescent phases (Pearson's R 0.81 and 0.72, respectively). Due to the slowly waning titer of anti-NP antibodies, the correlation with PRNT titer at the convalescent phase was poor. In conclusion, semi-quantitative immunoassay kits targeting the RBD showed neutralizing activity that was correlated by titer; measurement of anti-NP antibodies would be useful for determining past infections.

Keywords: COVID-19; SARS-CoV-2; antibody responses; immunoassay; neutralizing antibody; nucleopcapsid (NP) protein; serology; spike (S) protein.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Receiver operating characteristic (ROC) curves and area under curve (AUC) for each method (A) using positive and negative controls and (B–D) compared to PRNT ND50 of (B) ≥ 20, (C) ≥ 40, and (D) ≥ 80, respectively.
Figure 2
Figure 2
Serial kinetics of antibody titers measured with each method: (A) PRNT ND50, (B.) GenScript cPass sVNT, (C) Roche Elecsys Anti-SARS-CoV-2, (D) Roche Elecsys Anti-SARS-CoV2 S, and (E) Abbott AdviseDx SARS-CoV2 IgG II.
Figure 3
Figure 3
Scatter plot and Pearson’s correlation for each method grouped with acute/convalescent phase. (A) GenScript cPass sVNT, (B) Roche Elecsys Anti-SARS-CoV-2, (C) Roche Elecsys Anti-SARS-CoV2 S, and (D) Abbott AdviseDx SARS-CoV2 IgG II were compared with PRNT, respectively. Each colored line depicts the linear regression model and the surrounding grey-colored area represents the 95% confidence interval.
See this image and copyright information in PMC

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