Clinical Utility of SARS-CoV-2 Antibody Titer Multiplied by Binding Avidity of Receptor-Binding Domain (RBD) in Monitoring Protective Immunity and Clinical Severity
Etsuhisa Takahashi,
Takako Sawabuchi,
Tetsuya Homma,
Yosuke Fukuda,
Hironori Sagara,
Takeshi Kinjo,
Kaori Fujita,
Shigeru Suga,
Takashi Kimoto,
Satoko Sakai,
Keiko Kameda,
Hiroshi Kido
Affiliations
Etsuhisa Takahashi
Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Tokushima 770-8503, Japan
Takako Sawabuchi
Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Tokushima 770-8503, Japan
Tetsuya Homma
Division of Respiratory Medicine & Allergology, Showa University School of Medicine, Tokyo 142-8666, Japan
Yosuke Fukuda
Division of Respiratory Medicine & Allergology, Showa University School of Medicine, Tokyo 142-8666, Japan
Hironori Sagara
Division of Respiratory Medicine & Allergology, Showa University School of Medicine, Tokyo 142-8666, Japan
Takeshi Kinjo
First Department of Internal Medicine, Division of Infectious, Respiratory, and Digestive Medicine, University of the Ryukyu Graduate School of Medicine, Okinawa 903-0215, Japan
Kaori Fujita
Division of Pulmonary Medicine, National Hospital Organization Okinawa National Hospital, Okinawa 901-2214, Japan
Shigeru Suga
National Hospital Organization Mie National Hospital, Mie 514-0125, Japan
Takashi Kimoto
Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Tokushima 770-8503, Japan
Satoko Sakai
Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Tokushima 770-8503, Japan
Keiko Kameda
Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Tokushima 770-8503, Japan
Hiroshi Kido
Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Tokushima 770-8503, Japan
Conventional serum antibody titer, which expresses antibody level, does not provide antigen binding avidity of the variable region of the antibody, which is essential for the defense response to infection. Here, we quantified anti-SARS-CoV-2 antibody binding avidity to the receptor-binding domain (RBD) by competitive binding-inhibition activity (IC50) between SARS-CoV-2 S1 antigen immobilized on the DCP microarray and various RBD doses added to serum and expressed as 1/IC50 nM. The binding avidity analyzed under equilibrium conditions of antigen–antibody binding reaction is different from the avidity index measured with the chaotropic agent, such as urea, under nonequilibrium and short-time conditions. Quantitative determination of the infection-protection potential of antibodies was assessed by ABAT (antigen binding avidity antibody titer), which was calculated by the quantity (level) × quality (binding avidity) of antibodies. The binding avidity correlated strongly (r = 0.811) with cell-based virus-neutralizing activity. Maturation of the protective antibody induced by repeated vaccinations or SARS-CoV-2 infection was classified into three categories of ABAT, such as an initial, low, and high ABAT. Antibody maturity correlated with the clinical severity of COVID-19. Once a mature high binding avidity was achieved, it was maintained for at least 6–8 months regardless of the subsequent change in the antibody levels.