Features of the humoral and cellular immune response to S- and N-proteins of the SARS-CoV-2 virus

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Abstract

The pandemic of a new coronavirus infection, which has lasted for more than 3 years, is still accompanied by frequent mutations in the S-protein of the SARS-CoV-2 virus and the emergence of new variants of the virus, causing new outbreaks of the disease. Of all the coronavirus proteins, the S- and N-proteins are the most immunogenic. The aim of this study was to compare the features of humoral and T-cell immune responses to the SARS-CoV-2 S- and N-protein in people with different histories of interaction with this virus. The following were examined: 27 people who had COVID-19, 23 twice vaccinated with the Sputnik V vaccine and did not have COVID-19, 22 people who had COVID-19, and after 6-12 months twice vaccinated with the Sputnik V vaccine, and 25 people who recovered from COVID-19 twice. The level of antibodies was determined by enzyme immunoassay, cellular immunity was determined by the expression of CD107a on CD8high lymphocytes after they recognized antigens of the SARS-CoV-2 virus. It has been shown that the humoral immune response to the N-protein is 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 is represented by both short-lived plasma cells formed at the beginning of the response (IgG1 and IgG3 subclasses) and long-lived plasma cells (IgG1 subclass). The dynamics of the level of antibodies synthesized by short-lived plasma cells is described by the Fisher equation, and the Erlang equation is more suitable for describing the level of antibodies synthesized by long-lived plasma cells. The level of antibodies in the groups with hybrid immunity exceeds the level with post-vaccination immunity, and in the group with breakthrough immunity it exceeds both post-infection and post-vaccination immunity. Cellular immunity to the S- and N-proteins of the SARS-CoV-2 virus differs somewhat depending on the methods of induction of this immunity (vaccination or disease). Importantly, heterologous CD8+ T cell immune responses to the N-protein of other coronaviruses may be involved in immune defense against SARS-CoV-2.

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About the authors

Z. E. Afridonova

Gabrichevsky Research Institute for Epidemiology and Microbiology

Author for correspondence.
Email: toptyginaanna@rambler.ru
Russian Federation, 125212, Moscow

A. P. Toptygina

Gabrichevsky Research Institute for Epidemiology and Microbiology; Lomonosov Moscow State University

Email: toptyginaanna@rambler.ru
Russian Federation, 125212, Moscow; 119991, Moscow

I. S. Mikhaylov

Federal State Budgetary Educational Institution of Higher Education National Research University “MPEI”

Email: toptyginaanna@rambler.ru
Russian Federation, 111250, Moscow

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2. Fig. 1. The level of IgG antibodies to SARS-CoV-2 virus antigens. Curves: 1 – IgG antibodies to the N-protein of the SARS-CoV-2 virus (experimental data); 2 – IgG antibodies to the S-protein of the SARS-CoV-2 virus (experimental data); 3 – Fisher approximation of the level of IgG antibodies to the N-protein of the SARS-CoV-2 virus (short-lived plasmocytes); 4 – Fisher approximation of the level of IgG antibodies to the S-protein of the SARS-CoV-2 virus (short-lived plasmocytes); 5 – Erlang approximation of the level of IgG antibodies to the S-protein of the SARS-CoV-2 virus (long-lived plasmocytes)

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3. Fig. 2. Dynamics of the spectrum of IgG subclasses of antibodies to SARS-CoV-2 virus antigens. a – N is the protein of the SARS-CoV-2 virus; b – S is the protein of the SARS-CoV-2 virus

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4. Fig. 3. Comparison of IgG antibody levels to N- and S-protein in patients with COVID-19 (group 1), twice vaccinated with Sputnik V (group 2), who were ill, and after vaccinated with Sputnik V (group 3) and twice with COVID-19 (group 4)

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5. Fig. 4. Contribution of the IgG1 antibody subclass to the overall Ig response to the N- and S-protein of the SARS-CoV-2 virus

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6. Fig. 5. Cellular immune response to the N- and S-protein of the SARS-CoV-2 virus

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