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.