Differential patterns of antibody response against SARS-CoV-2 nucleocapsid epitopes detected in sera from patients in the acute phase of COVID-19, convalescents, and pre-pandemic individuals.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already infected more than 0.7 billion people and caused over 7 million deaths worldwide. At the same time, our knowledge about this virus is still incipient. In some cases, there is pre-pandemic immunity; however, its source is unknown. The analysis of patients' humoral responses might shed light on this puzzle. In this paper, we evaluated the antibody recognition of nucleocapsid protein, one of the structural proteins of SARS-CoV-2. For this purpose, we used pre-pandemic acute COVID-19 and convalescent patients' sera to identify and map nucleocapsid protein epitopes. We identified a common epitope KKSAAEASKKPRQKRTATKA recognized by sera antibodies from all three groups. Some motifs of this sequence are widespread among various coronaviruses, plants or human proteins indicating that there might be more sources of nucleocapsid-reactive antibodies than previous infections with seasonal coronavirus. The two sequences MSDNGPQNQRNAPRITFGGP and KADETQALPQRQKKQQTVTL were detected as specific for sera from patients in the acute phase of infection and convalescents making them suitable for future development of vaccines against SARS-CoV-2. Knowledge of the humoral response to SARS-CoV-2 infection is essential for the design of appropriate diagnostic tools and vaccine antigens.