RESUMEN
The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection- and vaccination-induced antibodies, highlighting the demands for research on the continuing discovery of broadly neutralizing antibodies (bnAbs). Here, we developed a panel of bnAbs against Omicron and other variants of concern (VOCs) elicited by vaccination of adenovirus-vectored COVID-19 vaccine (Ad5-nCoV). We also investigated the human longitudinal antibody responses following vaccination and demonstrated how the bnAbs evolved over time. A monoclonal antibody (mAb), named ZWD12, exhibited potent and broad neutralization against SARS-CoV-2 variants Alpha, Beta, Gamma, Kappa, Delta, and Omicron by blocking the spike protein binding to the angiotensin-converting enzyme 2 (ACE2) and provided complete protection in the challenged prophylactic and therapeutic K18-hACE2 transgenic mouse model. We defined the ZWD12 epitope by determining its structure in complex with the spike (S) protein via cryo-electron microscopy. This study affords the potential to develop broadly therapeutic mAb drugs and suggests that the RBD epitope bound by ZWD12 is a rational target for the design of a broad spectrum of vaccines.
Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , Anticuerpos Monoclonales/genética , Anticuerpos Antivirales , Anticuerpos ampliamente neutralizantes , COVID-19/prevención & control , Vacunas contra la COVID-19/genética , Microscopía por Crioelectrón , Epítopos , Humanos , Ratones , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/genética , Vacunación , Proteínas del Envoltorio ViralRESUMEN
Developing therapeutics against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be guided by the distribution of epitopes, not only on the receptor binding domain (RBD) of the Spike (S) protein but also across the full Spike (S) protein. We isolated and characterized monoclonal antibodies (mAbs) from 10 convalescent COVID-19 patients. Three mAbs showed neutralizing activities against authentic SARS-CoV-2. One mAb, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2 but does not bind the RBD. We defined the epitope of 4A8 as the N-terminal domain (NTD) of the S protein by determining with cryo-eletron microscopy its structure in complex with the S protein to an overall resolution of 3.1 angstroms and local resolution of 3.3 angstroms for the 4A8-NTD interface. This points to the NTD as a promising target for therapeutic mAbs against COVID-19.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Betacoronavirus/inmunología , Infecciones por Coronavirus/inmunología , Neumonía Viral/inmunología , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/inmunología , Adulto , Enzima Convertidora de Angiotensina 2 , Animales , Anticuerpos Monoclonales/sangre , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/metabolismo , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/química , Anticuerpos Neutralizantes/metabolismo , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/química , Anticuerpos Antivirales/metabolismo , Afinidad de Anticuerpos , Especificidad de Anticuerpos , Antígenos Virales/inmunología , Linfocitos B/inmunología , COVID-19 , Chlorocebus aethiops , Infecciones por Coronavirus/terapia , Proteínas de la Nucleocápside de Coronavirus , Microscopía por Crioelectrón , Ensayo de Inmunoadsorción Enzimática , Genes de las Cadenas Pesadas de las Inmunoglobulinas , Humanos , Memoria Inmunológica , Persona de Mediana Edad , Mutación , Proteínas de la Nucleocápside/inmunología , Pandemias , Peptidil-Dipeptidasa A/metabolismo , Fosfoproteínas , Neumonía Viral/terapia , Dominios Proteicos , Dominios y Motivos de Interacción de Proteínas/inmunología , Receptores de Coronavirus , Receptores Virales/metabolismo , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/metabolismo , Células Vero , Adulto JovenRESUMEN
A maternal woman was positive for SARS-CoV-2 tested in throat swabs but negative tested in other body fluids, and she had IgG and IgA detected in breast milk. Her infant negative for SARS-CoV-2 at birth had elevated IgG in serum but quickly decayed. These findings suggest that breastfeeding might have the potential benefit to the neonates.
Asunto(s)
Anticuerpos Antivirales/análisis , Betacoronavirus/inmunología , Infecciones por Coronavirus/inmunología , Leche Humana/inmunología , Neumonía Viral/inmunología , Complicaciones Infecciosas del Embarazo/virología , Adulto , Anticuerpos Antivirales/inmunología , COVID-19 , China , Femenino , Humanos , Inmunoglobulina A/análisis , Inmunoglobulina G/análisis , Recién Nacido , Leche Humana/virología , Pandemias , Embarazo , Complicaciones Infecciosas del Embarazo/inmunología , SARS-CoV-2RESUMEN
To determine distribution of severe acute respiratory syndrome coronavirus 2 in hospital wards in Wuhan, China, we tested air and surface samples. Contamination was greater in intensive care units than general wards. Virus was widely distributed on floors, computer mice, trash cans, and sickbed handrails and was detected in air ≈4 m from patients.