ABSTRACT
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.
Subject(s)
COVID-19 , Communicable Diseases , Vaccines , Humans , COVID-19 Vaccines , Spike Glycoprotein, Coronavirus , COVID-19/prevention & control , SARS-CoV-2 , T-Lymphocytes , Adenoviridae/geneticsABSTRACT
Two new alleles B*18:01:01:74 and C*06:02:01:93 identified in Russian individuals.
Subject(s)
HLA-C Antigens , High-Throughput Nucleotide Sequencing , Humans , HLA-C Antigens/genetics , Alleles , HLA-B Antigens/genetics , RussiaABSTRACT
Two new alleles HLA-A*26:01:01:53 and DRB1*01:141 identified in Russian individuals.
Subject(s)
HLA-A Antigens , High-Throughput Nucleotide Sequencing , Humans , HLA-DRB1 Chains/genetics , Alleles , Russia , HLA-A Antigens/geneticsABSTRACT
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.
Subject(s)
HLA-A Antigens , High-Throughput Nucleotide Sequencing , Alleles , HLA-A Antigens/genetics , HLA-B Antigens/genetics , Humans , RussiaABSTRACT
Two new alleles A*02:01:01:208 and DQB1*06:03:44 identified in Russian individuals.
Subject(s)
HLA-A Antigens , High-Throughput Nucleotide Sequencing , Alleles , HLA-DQ beta-Chains/genetics , Humans , RussiaABSTRACT
Four new alleles HLA-A*68:288, C*07:1012, C*12:364, and DQA1*05:51 discovered in Russian individuals.
Subject(s)
HLA-A Antigens , Alleles , HLA-A Antigens/genetics , HLA-DQ alpha-Chains/genetics , Humans , RussiaABSTRACT
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.
