tetano
Editor, Senior Moderator
mSphere
. 2022 Feb 2;e0088321.
doi: 10.1128/msphere.00883-21. Online ahead of print.
Quantifying Neutralizing Antibodies in Patients with COVID-19 by a Two-Variable Generalized Additive Model
Kuan-Ting Liu[SUP] #[/SUP][SUP] 1 2 [/SUP], Yu-Nong Gong[SUP] #[/SUP][SUP] 1 3 [/SUP], Chung-Guei Huang[SUP] #[/SUP][SUP] 3 4 [/SUP], Peng-Nien Huang[SUP] #[/SUP][SUP] 1 5 [/SUP], Kar-Yee Yu[SUP] 1 2 [/SUP], Hou-Chen Lee[SUP] 1 6 [/SUP], Sun-Che Lee[SUP] 1 7 [/SUP], Huan-Jung Chiang[SUP] 1 [/SUP], Yu-An Kung[SUP] 1 [/SUP], Yueh-Te Lin[SUP] 1 2 3 [/SUP], Mei-Jen Hsiao[SUP] 3 [/SUP], Po-Wei Huang[SUP] 3 [/SUP], Sheng-Yu Huang[SUP] 1 2 [/SUP], Hsin-Tai Wu[SUP] 1 [/SUP], Chih-Ching Wu[SUP] 1 2 4 8 [/SUP], Rei-Lin Kuo[SUP] 1 2 4 9 [/SUP], Kuan-Fu Chen[SUP] 10 11 12 [/SUP], Chuan-Tien Hung[SUP] 13 [/SUP], Kasopefoluwa Y Oguntuyo[SUP] 13 [/SUP], Christian S Stevens[SUP] 13 [/SUP], Shreyas Kowdle[SUP] 13 [/SUP], Hsin-Ping Chiu[SUP] 13 [/SUP], Benhur Lee[SUP] 13 [/SUP], Guang-Wu Chen[SUP] 1 3 14 15 [/SUP], Shin-Ru Shih[SUP] 1 3 4 16 [/SUP]
Affiliations
Abstract
Considering the urgent demand for faster methods to quantify neutralizing antibody titers in patients with coronavirus (CoV) disease 2019 (COVID-19), developing an analytical model or method to replace the conventional virus neutralization test (NT) is essential. Moreover, a "COVID-19 immunity passport" is currently being proposed as a certification for people who travel internationally. Therefore, an enzyme-linked immunosorbent assay (ELISA) was designed to detect severe acute respiratory syndrome CoV 2 (SARS-CoV-2)-neutralizing antibodies in serum, which is based on the binding affinity of SARS-CoV-2 viral spike protein 1 (S1) and the viral spike protein receptor-binding domain (RBD) to antibodies. The RBD is considered the major binding region of neutralizing antibodies. Furthermore, S1 covers the RBD and several other regions, which are also important for neutralizing antibody binding. In this study, we assessed 144 clinical specimens, including those from patients with PCR-confirmed SARS-CoV-2 infections and healthy donors, using both the NT and ELISA. The ELISA results analyzed by spline regression and the two-variable generalized additive model precisely reflected the NT value, and the correlation between predicted and actual NT values was as high as 0.917. Therefore, our method serves as a surrogate to quantify neutralizing antibody titer. The analytic method and platform used in this study present a new perspective for serological testing of SARS-CoV-2 infection and have clinical potential to assess vaccine efficacy. IMPORTANCE Herein, we present a new approach for serological testing for SARS-CoV-2 antibodies using innovative laboratory methods that demonstrate a combination of biology and mathematics. The traditional virus neutralization test is the gold standard method; however, it is time-consuming and poses a risk to medical personnel. Thus, there is a demand for methods that rapidly quantify neutralizing antibody titers in patients with COVID-19 or examine vaccine efficacy at a biosafety level 2 containment facility. Therefore, we used a two-variable generalized additive model to analyze the results of the enzyme-linked immunosorbent assay and found the method to serve as a surrogate to quantify neutralizing antibody titers. This methodology has potential for clinical use in assessing vaccine efficacy.
Keywords: SARS-CoV-2; enzyme-linked immunosorbent assay; neutralizing antibody; receptor-binding domain; spike protein; two-variable generalized additive model.
. 2022 Feb 2;e0088321.
doi: 10.1128/msphere.00883-21. Online ahead of print.
Quantifying Neutralizing Antibodies in Patients with COVID-19 by a Two-Variable Generalized Additive Model
Kuan-Ting Liu[SUP] #[/SUP][SUP] 1 2 [/SUP], Yu-Nong Gong[SUP] #[/SUP][SUP] 1 3 [/SUP], Chung-Guei Huang[SUP] #[/SUP][SUP] 3 4 [/SUP], Peng-Nien Huang[SUP] #[/SUP][SUP] 1 5 [/SUP], Kar-Yee Yu[SUP] 1 2 [/SUP], Hou-Chen Lee[SUP] 1 6 [/SUP], Sun-Che Lee[SUP] 1 7 [/SUP], Huan-Jung Chiang[SUP] 1 [/SUP], Yu-An Kung[SUP] 1 [/SUP], Yueh-Te Lin[SUP] 1 2 3 [/SUP], Mei-Jen Hsiao[SUP] 3 [/SUP], Po-Wei Huang[SUP] 3 [/SUP], Sheng-Yu Huang[SUP] 1 2 [/SUP], Hsin-Tai Wu[SUP] 1 [/SUP], Chih-Ching Wu[SUP] 1 2 4 8 [/SUP], Rei-Lin Kuo[SUP] 1 2 4 9 [/SUP], Kuan-Fu Chen[SUP] 10 11 12 [/SUP], Chuan-Tien Hung[SUP] 13 [/SUP], Kasopefoluwa Y Oguntuyo[SUP] 13 [/SUP], Christian S Stevens[SUP] 13 [/SUP], Shreyas Kowdle[SUP] 13 [/SUP], Hsin-Ping Chiu[SUP] 13 [/SUP], Benhur Lee[SUP] 13 [/SUP], Guang-Wu Chen[SUP] 1 3 14 15 [/SUP], Shin-Ru Shih[SUP] 1 3 4 16 [/SUP]
Affiliations
- PMID: 35107336
- DOI: 10.1128/msphere.00883-21
Abstract
Considering the urgent demand for faster methods to quantify neutralizing antibody titers in patients with coronavirus (CoV) disease 2019 (COVID-19), developing an analytical model or method to replace the conventional virus neutralization test (NT) is essential. Moreover, a "COVID-19 immunity passport" is currently being proposed as a certification for people who travel internationally. Therefore, an enzyme-linked immunosorbent assay (ELISA) was designed to detect severe acute respiratory syndrome CoV 2 (SARS-CoV-2)-neutralizing antibodies in serum, which is based on the binding affinity of SARS-CoV-2 viral spike protein 1 (S1) and the viral spike protein receptor-binding domain (RBD) to antibodies. The RBD is considered the major binding region of neutralizing antibodies. Furthermore, S1 covers the RBD and several other regions, which are also important for neutralizing antibody binding. In this study, we assessed 144 clinical specimens, including those from patients with PCR-confirmed SARS-CoV-2 infections and healthy donors, using both the NT and ELISA. The ELISA results analyzed by spline regression and the two-variable generalized additive model precisely reflected the NT value, and the correlation between predicted and actual NT values was as high as 0.917. Therefore, our method serves as a surrogate to quantify neutralizing antibody titer. The analytic method and platform used in this study present a new perspective for serological testing of SARS-CoV-2 infection and have clinical potential to assess vaccine efficacy. IMPORTANCE Herein, we present a new approach for serological testing for SARS-CoV-2 antibodies using innovative laboratory methods that demonstrate a combination of biology and mathematics. The traditional virus neutralization test is the gold standard method; however, it is time-consuming and poses a risk to medical personnel. Thus, there is a demand for methods that rapidly quantify neutralizing antibody titers in patients with COVID-19 or examine vaccine efficacy at a biosafety level 2 containment facility. Therefore, we used a two-variable generalized additive model to analyze the results of the enzyme-linked immunosorbent assay and found the method to serve as a surrogate to quantify neutralizing antibody titers. This methodology has potential for clinical use in assessing vaccine efficacy.
Keywords: SARS-CoV-2; enzyme-linked immunosorbent assay; neutralizing antibody; receptor-binding domain; spike protein; two-variable generalized additive model.