RESUMEN
The B and T lymphocytes of the adaptive immune system are important for the control of most viral infections, including COVID-19. Identification of epitopes recognized by these cells is fundamental for understanding how the immune system detects and removes pathogens, and for antiviral vaccine design. Intriguingly, several cross-reactive T lymphocyte epitopes from SARS-CoV-2 with other betacoronaviruses responsible for the common cold have been identified. In addition, antibodies that cross-recognize the spike protein, but not the nucleoprotein (N protein), from different betacoronavirus have also been reported. Using a consensus of eight bioinformatic methods for predicting B-cell epitopes and the collection of experimentally detected epitopes for SARS-CoV and SARS-CoV-2, we identified four surface-exposed, conserved, and hypothetical antigenic regions that are exclusive of the N protein. These regions were analyzed using ELISA assays with two cohorts: SARS-CoV-2 infected patients and pre-COVID-19 samples. Here we describe four epitopes from SARS-CoV-2 N protein that are recognized by the humoral response from multiple individuals infected with COVID-19, and are conserved in other human coronaviruses. Three of these linear surface-exposed sequences and their peptide homologs in SARS-CoV-2 and HCoV-OC43 were also recognized by antibodies from pre-COVID-19 serum samples, indicating cross-reactivity of antibodies against coronavirus N proteins. Different conserved human coronaviruses (HCoVs) cross-reactive B epitopes against SARS-CoV-2 N protein are detected in a significant fraction of individuals not exposed to this pandemic virus. These results have potential clinical implications.
Asunto(s)
Proteínas de la Nucleocápside de Coronavirus/inmunología , Coronavirus Humano OC43/inmunología , Reacciones Cruzadas/inmunología , Mapeo Epitopo/métodos , Epítopos de Linfocito B/inmunología , SARS-CoV-2/inmunología , Adulto , Secuencia de Aminoácidos , COVID-19/inmunología , COVID-19/virología , Estudios de Cohortes , Proteínas de la Nucleocápside de Coronavirus/química , Proteínas de la Nucleocápside de Coronavirus/genética , Coronavirus Humano OC43/genética , Coronavirus Humano OC43/fisiología , Reacciones Cruzadas/genética , Ensayo de Inmunoadsorción Enzimática/métodos , Epítopos de Linfocito B/metabolismo , Células HEK293 , Personal de Salud/estadística & datos numéricos , Humanos , Dominios Proteicos , SARS-CoV-2/genética , SARS-CoV-2/fisiología , Homología de Secuencia de Aminoácido , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/inmunologíaRESUMEN
SARS-CoV-2 VOC immune evasion is mainly due to lower cross-reactivity from previously elicited class I/II neutralizing antibodies, while increased affinity to hACE2 plays a minor role. The affinity between antibodies and VOCs is impacted by remodeling of the electrostatic surface potential of the Spike RBDs. The P.3 variant is a putative VOC.
Asunto(s)
Anticuerpos Neutralizantes/inmunología , Afinidad de Anticuerpos/genética , Evasión Inmune/genética , SARS-CoV-2/inmunología , Afinidad de Anticuerpos/inmunología , Reacciones Cruzadas/genética , Modelos Moleculares , Dominios Proteicos , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/inmunología , Electricidad EstáticaRESUMEN
Recent studies have shown a significant level of T cell immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in convalescent coronavirus disease 2019 (COVID-19) patients and unexposed healthy individuals. Also, SARS-CoV-2-reactive T memory cells occur in unexposed healthy individuals from endemic coronaviruses that cause the 'common cold.' The finding of the expression of adaptive SARS-CoV-2-reactive T memory cells in unexposed healthy individuals may be due to multiple cross-reactive viral protein targets following previous exposure to endemic human coronavirus infections. The opinion of the authors is that determination of protein sequence homologies across seemingly disparate viral protein libraries may provide epitope-matching data that link SARS-CoV-2-reactive T memory cell signatures to prior administration of cross-reacting vaccines to common viral pathogens. Exposure to SARS-CoV-2 initiates diverse cellular immune responses, including the associated 'cytokine storm'. Therefore, it is possible that the intact virus possesses a required degree of conformational matching, or stereoselectivity, to effectively target its receptor on multiple cell types. Therefore, conformational matching may be viewed as an evolving mechanism of viral infection and viral replication by an evolutionary modification of the angiotensin-converting enzyme 2 (ACE2) receptor required for SARS-CoV-2 binding and host cell entry. The authors propose that convalescent memory T cell immunity in individuals with mild or asymptomatic SARS-CoV-2 infection may result from an evolutionarily adapted immune response to coronavirus and the 'common cold'.