RESUMEN
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.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , COVID-19/inmunología , Epítopos de Linfocito T/metabolismo , SARS-CoV-2/fisiología , Glicoproteína de la Espiga del Coronavirus/metabolismo , Adolescente , Adulto , Anticuerpos Antivirales/metabolismo , Infecciones Asintomáticas , Células Cultivadas , Convalecencia , Epítopos de Linfocito T/inmunología , Femenino , Humanos , Inmunidad , Memoria Inmunológica , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Pandemias , Receptores de Antígenos de Linfocitos T/metabolismo , Glicoproteína de la Espiga del Coronavirus/inmunología , Adulto JovenRESUMEN
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.
Asunto(s)
COVID-19 , Enfermedades Transmisibles , Vacunas , Humanos , Vacunas contra la COVID-19 , Glicoproteína de la Espiga del Coronavirus , COVID-19/prevención & control , SARS-CoV-2 , Linfocitos T , Adenoviridae/genéticaRESUMEN
Two new alleles HLA-A*26:01:01:53 and DRB1*01:141 identified in Russian individuals.
Asunto(s)
Antígenos HLA-A , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Cadenas HLA-DRB1/genética , Alelos , Federación de Rusia , Antígenos HLA-A/genéticaRESUMEN
Two new alleles B*18:01:01:74 and C*06:02:01:93 identified in Russian individuals.
Asunto(s)
Antígenos HLA-C , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Antígenos HLA-C/genética , Alelos , Antígenos HLA-B/genética , Federación de RusiaRESUMEN
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.
Asunto(s)
Antígenos HLA-A , Secuenciación de Nucleótidos de Alto Rendimiento , Alelos , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Humanos , Federación de RusiaRESUMEN
Two new alleles A*02:01:01:208 and DQB1*06:03:44 identified in Russian individuals.
Asunto(s)
Antígenos HLA-A , Secuenciación de Nucleótidos de Alto Rendimiento , Alelos , Cadenas beta de HLA-DQ/genética , Humanos , Federación de RusiaRESUMEN
Four new alleles HLA-A*68:288, C*07:1012, C*12:364, and DQA1*05:51 discovered in Russian individuals.