Clonal structure and the specificity of vaccine-induced T cell response to SARS-CoV-2 Spike protein.

Adenovirus vaccines, particularly the COVID-19 Ad5-nCoV adenovirus vaccine, have emerged as promising tools in the fight against infectious diseases. In this study, we investigated the structure of the T cell response to the Spike protein of the SARS-CoV-2 virus used in the COVID-19 Ad5-nCoV adenoviral vaccine in a phase 3 clinical trial (NCT04540419). In 69 participants, we collected peripheral blood samples at four time points after vaccination or placebo injection. Sequencing of T cell receptor repertoires from Spike-stimulated T cell cultures at day 14 from 17 vaccinated revealed a more diverse CD4+ T cell repertoire compared to CD8+. Nevertheless, CD8+ clonotypes accounted for more than half of the Spike-specific repertoire. Our longitudinal analysis showed a peak T cell response at day 14, followed by a decline until month 6. Remarkably, multiple T cell clonotypes persisted for at least 6 months after vaccination, as demonstrated by ex vivo stimulation. Examination of CDR3 regions revealed homologous sequences in both CD4+ and CD8+ clonotypes, with major CD8+ clonotypes sharing high similarity with annotated sequences specific for the NYNYLYRLF peptide, suggesting potential immunodominance. In conclusion, our study demonstrates the immunogenicity of the Ad5-nCoV adenoviral vaccine and highlights its ability to induce robust and durable T cell responses. These findings provide valuable insight into the efficacy of the vaccine against COVID-19 and provide critical information for ongoing efforts to control infectious diseases.

The novel HLA-B*35:01:77 allele identified in a Russian volunteer bone marrow donor.

Nucleotide substitutions in the 5'UTR and exon 2 of HLA-B*35:01:01:05 result in a novel allele, HLA-B*35:01:77.

Characterization of two new HLA alleles, HLA-B*18:01:01:74 and HLA-C*06:02:01:93 in Russian individuals.

Two new alleles B*18:01:01:74 and C*06:02:01:93 identified in Russian individuals.

Characterization of two novel HLA alleles: HLA-A*26:01:01:53 and -DRB1*01:141.

Two new alleles HLA-A*26:01:01:53 and DRB1*01:141 identified in Russian individuals.

Four new HLA class I alleles: HLA-A*03:445, -A*66:44, -B*35:01:70, and -C*07:02:01:161 identified in Russians.

Identification of four new alleles A*03:445, A*66:44, B*35:01:70, and C*07:02:01:161 by next-generation sequencing.

Characterization of two new HLA alleles, HLA-A*02:01:01:208 and HLA-DQB1*06:03:44.

Two new alleles A*02:01:01:208 and DQB1*06:03:44 identified in Russian individuals.

Characterization of four new HLA alleles: HLA-A*68:288, -C*07:1012, -C*13:364, and -DQA1*05:51.

Four new alleles HLA-A*68:288, C*07:1012, C*12:364, and DQA1*05:51 discovered in Russian individuals.

Immunogenic epitope panel for accurate detection of non-cross-reactive T cell response to SARS-CoV-2.

The ongoing COVID-19 pandemic calls for more effective diagnostic tools. T cell response assessment serves as an independent indicator of prior COVID-19 exposure while also contributing to a more comprehensive characterization of SARS-CoV-2 immunity. In this study, we systematically assessed the immunogenicity of 118 epitopes with immune cells collected from multiple cohorts of vaccinated, convalescent, healthy unexposed, and SARS-CoV-2-exposed donors. We identified 75 immunogenic epitopes, 24 of which were immunodominant. We further confirmed HLA restriction for 49 epitopes and described association with more than 1 HLA allele for 14 of these. Exclusion of 2 cross-reactive epitopes that generated a response in prepandemic samples left us with a 73-epitope set that offered excellent diagnostic specificity without losing sensitivity compared with full-length antigens, and this evoked a robust cross-reactive response. We subsequently incorporated this set of epitopes into an in vitro diagnostic Corona-T-test, which achieved a diagnostic accuracy of 95% in a clinical trial. In a cohort of asymptomatic seronegative individuals with a history of prolonged SARS-CoV-2 exposure, we observed a complete absence of T cell response to our epitope panel. In combination with strong reactivity to full-length antigens, this suggests that a cross-reactive response might protect these individuals.

HLA-A*24:521 and HLA-B*13:152 identified by next-generation sequencing in Russian bone marrow donors.

Two novel alleles, HLA-A*24:521 and HLA-B*13:152, are characterized.

Two novel HLA alleles identified in Russian bone marrow donors: HLA-A*02:957 and -C*12:03:67.

Characterization of two novel HLA class I alleles, A*02:957 and C*12:03:67.

SARS-CoV-2 Epitopes Are Recognized by a Public and Diverse Repertoire of Human T Cell Receptors.

Understanding the hallmarks of the immune response to SARS-CoV-2 is critical for fighting the COVID-19 pandemic. We assessed antibody and T cell reactivity in convalescent COVID-19 patients and healthy donors sampled both prior to and during the pandemic. Healthy donors examined during the pandemic exhibited increased numbers of SARS-CoV-2-specific T cells, but no humoral response. Their probable exposure to the virus resulted in either asymptomatic infection without antibody secretion or activation of preexisting immunity. In convalescent patients, we observed a public and diverse T cell response to SARS-CoV-2 epitopes, revealing T cell receptor (TCR) motifs with germline-encoded features. Bulk CD4+ and CD8+ T cell responses to the spike protein were mediated by groups of homologous TCRs, some of them shared across multiple donors. Overall, our results demonstrate that the T cell response to SARS-CoV-2, including the identified set of TCRs, can serve as a useful biomarker for surveying antiviral immunity.

The novel HLA-A*26:01:64 allele, identified by next-generation sequencing in a bone marrow donor of Bashkir origin.

HLA-A*26:01:64 has one nucleotide difference from HLA-A*26:01: 01:01 at gDNA position 989 (G→A).

Allele and haplotype frequencies of HLA-A, -B, -C, -DRB1, -DQB1 in Northern Ossetians from Vladikavkaz, Russia.

This report shows the HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype frequencies in a population of 127 healthy Ossetian donors of blood marrow from Vladikavkaz, Russia. First- and second-field (for HLA-C locus) HLA genotyping was performed by polymerase chain reaction sequence-specific priming and/or oligonucleotide probes. Statistical analysis were performed using gene counting and Arlequin software packages. There was no deviation from Hardy-Weinberg equilibrium for all tested loci. The HLA genotypic and haplotypic data of the Ossetians reported here are available in free access at the Allele Frequencies Net Database (http://www.allelefrequencies.net). This data can serve as a reference database for further HLA-based studies in population genetics.

Immunogenetic Factors of Predisposition to Blood Malignancies in Russian Population.

HLA class II loci (DRB1, DQB1) have been investigated in patients with different blood tumors: acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia and Hodgkin's disease. The purpose was to determine the general (common) markers of predisposition (or resistance) in HLA class II loci to malignant changing of hemopoiesis in Russian population, and to verify the individual associations between HLA and disease for each examined neoplasm. It has been found that: 1). DRB1*11 is general (common) factor of predisposition to all investigated blood neoplasms. 2). In HLA class II loci there are factors of predisposition to one-third of neoplasms such as DRB1*12 DQB1*0503, 0301 for acute lymphoblastic leukemia, DRB1*14, DQB1*0503, 0601 for chronic myelogenous leukemia, DQB1*0503 and 0301 for Hodgkin's disease. Our findings support the hypothesis that there are structures associated with HLA system, which predispose to malignant change of hemopoiesis in general, and other HLA structures, which "turn" the change into concrete nosological form. Both factors are linked with HLA class II loci.