Clonal diversity determines persistence of SARS-CoV-2 epitope-specific T cell response

T cells play a pivotal role in reducing disease severity during SARS-CoV-2 infection and formation of long-term immune memory. We studied 50 COVID-19 convalescent patients and found that T cell response was induced more frequently and persisted longer than circulating antibodies. To identify epitopes that give rise to long-lived T cell memory, we performed ex vivo T cell expansion, MHC-tetramer cell-sorting, and high-throughput sequencing. We identified 756 clonotypes specific to nine known CD8+ T cell receptor (TCR) epitopes. Some epitopes were recognized by highly similar public clonotypes with restricted variable and joining segment usage. Receptors for other epitopes were extremely diverse, suggesting alternative modes of recognition. We also tracked persistence of epitope-specific response and individual clonotypes for a median of eight months after infection. The number of recognized epitopes per patient and quantity of epitope-specific clonotypes decreased over time, but the studied epitopes were characterized by uneven decline in the number of specific T cells. Epitopes with more clonally diverse TCR repertoires induced more pronounced and durable responses. In contrast, the abundance of specific clonotypes in peripheral circulation had no influence on their persistence. Our study demonstrates the durability of SARS-CoV-2-specific CD8+ memory, and offers important implications for vaccine design.

Boosting of the SARS-CoV-2-specific immune response after vaccination with single-dose Sputnik Light vaccine

Despite the measures taken worldwide, COVID-19 pandemic still progresses. While efficient antiviral drugs are not yet widely available, vaccination is the best option to control the infection rate. Although this option is obvious in case of COVID-19-naive individuals, it is still unclear when individuals who have recovered from a previous SARS-CoV-2 infection should be vaccinated and whether the vaccination raises immune responses against the coronavirus and its novel variants. Here we measured the dynamics of the antibody and T-cell responses, as well as virus neutralizing activity (VNA) in serum against two SARS-CoV-2 variants, B.1.1.1 and B.1.617.2, among 84 individuals with different COVID-19 status who were vaccinated with Sputnik Light vaccine. We showed that vaccination of individuals previously exposed to the virus considerably boosts the existing immune response. In these individuals, RBD-specific IgG titers and VNA in serum were already elevated on the 7th day after vaccination, while COVID-19-naive individuals developed the antibody response and VNA mainly 21 days post-vaccination. Additionally, we found a strong correlation between RBD-specific IgG titers and VNA in serum, and according to these data vaccination may be recommended if the RBD-specific IgG titers drop to 142.7 BAU/mL or below. In summary, the results of the study demonstrate that vaccination is beneficial both for COVID-19-naive and recovered individuals, especially since it raises serum VNA against the B.1.617.2 variant - one of four the SARS-CoV-2 variants of concern.

A prospective study of the protective effect of SARS-CoV-2-specific antibodies and T cells in Moscow residents

Rapid spread of COVID-19 pandemic made a substantial share of the world population immunised by SARS-CoV-2 antigens. Infection induces the development of virus-specific antibodies and T cells. Ample evidence on the antibody-mediated protection is contrasted by the elusive role of T cells in preventing infection. To explore the impact of T cells and to quantify the protective levels of the immune responses we conducted a large prospective study: 5,340 Moscow residents were evaluated for the antibody and cellular immune responses to SARS-CoV-2 and monitored for COVID-19 up to 300 days. The antibody and cellular responses were tightly interconnected, their magnitude inversely correlated with infection probability. Similar maximal level of protection was reached by individuals positive for both types of responses and by individuals with antibodies alone. Meanwhile, T cells in the absence of antibodies provided an intermediate level of protection. The real-world data on the protective effects of T cells have important implications for T cell immunology and development of the strategies to fight the pandemic.