Longitudinal profiles of immunoglobulin G antibodies against severe acute respiratory syndrome coronavirus components and neutralizing activities in recovered patients

Background: Immunological memory is the basis for vaccination. Currently, the longitudinal profiles of antibody responses in recovered severe acute respiratory syndrome (SARS) patients have not been fully characterized. Methods: In this study we sequentially followed up 19 recovered SARS patients over a 3-y period in order to characterize the dynamic changes in antibody responses against viral components in detail. In addition, 4 blood samples were obtained at month 60. Results: We found that immunoglobulin G (IgG) antibodies and their neutralizing activities decreased throughout the entire phase of the study. For IgG antibodies in the 3rd y, the positive rate of whole-virus-specific antibodies was 42%, which was tested with commercial kits at 1/10 dilution of the sera. In comparison, the positive rate of spike (S) protein-specific antibodies was 100%, which was tested by spike protein-based ELISA at 1/100 dilution; 4 samples at month 60 were included. The average optical density (OD) reading of nucleocapsid (N) protein-specific antibodies fell dramatically between month 3 and month 12, and it decreased gradually at low levels that were a little higher than the cut-off value from month 12. For neutralizing antibodies, neutralizing activity was detectable in 89% of recovered patients in the 3rd y. S protein-specific IgG levels (r = 0.717) correlated better with neutralizing activity than SARS coronavirus-specific IgG levels (r = 0.571). Conclusions: These systematic findings provide valuable information on natural humoral memory responses, and the data will be helpful for understanding the pathogenesis of SARS coronavirus infection and for the rational design of vaccines.