Humoral and Cellular Immune Response to SARS-CoV-2 S and N Proteins

The pandemic of a new coronavirus infection that has lasted for more than 3 years, is still accompanied by frequent mutations in the S protein of SARS-CoV-2 and emergence of new virus variants causing new disease outbreak. Of all coronaviral proteins, the S and N proteins are the most immunogenic. The aim of this study was to compare the features of the humoral and T-cell immune responses to the SARS-CoV-2 S and N proteins in people with different histories of interaction with this virus. The study included 27 individuals who had COVID-19 once, 23 people who were vaccinated twice with the Sputnik V vaccine and did not have COVID-19, 22 people who had COVID-19 and were vaccinated twice with Sputnik V 6-12 months after the disease, and 25 people who had COVID-19 twice. The level of antibodies was determined by the enzyme immunoassay, and the cellular immunity was assessed by the expression of CD107a on CD8^high lymphocytes after recognition of SARS-CoV-2 antigens. It was shown that the humoral immune response to the N protein was formed mainly by short-lived plasma cells synthesizing IgG antibodies of all four subclasses with a gradual switch from IgG3 to IgG1. The response to the S protein was formed by short-lived plasma cells at the beginning of the response (IgG1 and IgG3 subclasses) and then by long-lived plasma cells (IgG1 subclass). The dynamics of antibody level synthesized by the short-lived plasma cells was described by the Fisher equation, while changes in the level of antibodies synthesized by the long-lived plasma cells were described by the Erlang equation. The level of antibodies in the groups with the hybrid immunity exceeded that in the group with the post-vaccination immunity; the highest antibody content was observed in the group with the breakthrough immunity. The cellular immunity to the S and N proteins differed depending on the mode of immune response induction (vaccination or disease). Importantly, the response of heterologous CD8⁺ T cell to the N proteins of other coronaviruses may be involved in the immune defense against SARS-CoV-2.