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1.
Signal Transduct Target Ther ; 7(1): 139, 2022 04 27.
Article in English | MEDLINE | ID: covidwho-1815514

ABSTRACT

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.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Monoclonal/genetics , Antibodies, Viral , Broadly Neutralizing Antibodies , COVID-19/prevention & control , COVID-19 Vaccines/genetics , Cryoelectron Microscopy , Epitopes , Humans , Mice , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Vaccination , Viral Envelope Proteins
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324160

ABSTRACT

The unprecedented coronavirus disease 2019 (COVID-19) epidemic has created a worldwide public health emergency, and there is an urgent need to develop an effective vaccine to control this severe infectious disease. Here, we found that a single vaccination with a replication-defective human type 5 adenovirus encoding the SARS-CoV-2 spike protein (Ad5-nCoV) protected mice completely against SARS-CoV-2 infection in the upper and lower respiratory tracts. Additionally, a single vaccination with Ad5-nCoV protected ferrets from SARS-CoV-2 infection in the upper respiratory tract. This study suggested that a combination of intramuscular and mucosal vaccination maybe provide a desirable protective efficacy and different Ad5-nCoV delivery modes are worth further investigation in human clinical trials.

3.
Atmospheric Environment ; 259:118508, 2021.
Article in English | ScienceDirect | ID: covidwho-1252473

ABSTRACT

Aerosols greatly impact the global and regional climate system and public health. We conducted lidar measurements at Wuhan (30.53°N, 114.37°E) from October 2010 to June 2020 and analyzed the massive dataset with an automatic lidar processing algorithm, to investigate the long-term variations of aerosols. Lidar-derived total aerosol optical depth (AOD) at 532 nm shows an interannual decrease of −0.049 since 2010. Compared with AODs in other megacities worldwide, the AOD for Wuhan shows the largest decrease rate. After separating AOD contributions from boundary layer (BL) and free troposphere (FT), different evolution patterns are revealed with AOD decrease rates of −0.009 and −0.044 per year for FT and BL, respectively, which indicates more than 80% of AOD decrease are associated with reductions of local emissions. In addition, BL AOD was always larger than FT AOD before COVID-19 lockdown. However, this relation was conversed thereafter, with the lowest value of 0.125 for BL AOD since 2010, which is only the half of FT AOD within the same period. This feature corroborates strong influences of COVID-19 lockdown on human activities and local emissions. These findings can improve our understandings of regional aerosol responses to pollution controls and aerosol direct impacts on regional climate.

4.
Nat Commun ; 11(1): 4081, 2020 08 14.
Article in English | MEDLINE | ID: covidwho-717117

ABSTRACT

The unprecedented coronavirus disease 2019 (COVID-19) epidemic has created a worldwide public health emergency, and there is an urgent need to develop an effective vaccine to control this severe infectious disease. Here, we find that a single vaccination with a replication-defective human type 5 adenovirus encoding the SARS-CoV-2 spike protein (Ad5-nCoV) protect mice completely against mouse-adapted SARS-CoV-2 infection in the upper and lower respiratory tracts. Additionally, a single vaccination with Ad5-nCoV protects ferrets from wild-type SARS-CoV-2 infection in the upper respiratory tract. This study suggests that the mucosal vaccination may provide a desirable protective efficacy and this delivery mode is worth further investigation in human clinical trials.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/immunology , Animals , Antibodies, Viral/immunology , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/immunology , Disease Models, Animal , Drug Design , Female , Genetic Vectors , HEK293 Cells , Humans , Mice , Mice, Inbred BALB C , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Viral Vaccines/administration & dosage , Viral Vaccines/genetics
5.
Science ; 369(6504): 650-655, 2020 08 07.
Article in English | MEDLINE | ID: covidwho-610891

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Adult , Angiotensin-Converting Enzyme 2 , Animals , Antibodies, Monoclonal/blood , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/metabolism , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/metabolism , Antibodies, Viral/blood , Antibodies, Viral/chemistry , Antibodies, Viral/metabolism , Antibody Affinity , Antibody Specificity , Antigens, Viral/immunology , B-Lymphocytes/immunology , COVID-19 , Chlorocebus aethiops , Coronavirus Infections/therapy , Coronavirus Nucleocapsid Proteins , Cryoelectron Microscopy , Enzyme-Linked Immunosorbent Assay , Genes, Immunoglobulin Heavy Chain , Humans , Immunologic Memory , Middle Aged , Mutation , Nucleocapsid Proteins/immunology , Pandemics , Peptidyl-Dipeptidase A/metabolism , Phosphoproteins , Pneumonia, Viral/therapy , Protein Domains , Protein Interaction Domains and Motifs/immunology , Receptors, Coronavirus , Receptors, Virus/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells , Young Adult
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