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2.
Cell ; 185(13): 2265-2278.e14, 2022 06 23.
Article in English | MEDLINE | ID: covidwho-1803705

ABSTRACT

Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on the dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants. A prototype-Beta chimeric RBD-dimer was first designed to adapt the resistant Beta variant. Compared with its homotypic forms, the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice. The protection of the chimeric vaccine was further verified in macaques. This approach was generalized to develop Delta-Omicron chimeric RBD-dimer to adapt the currently prevalent variants. Again, the chimeric vaccine elicited broader sera neutralization of SARS-CoV-2 variants and conferred better protection against challenge by either Delta or Omicron SARS-CoV-2 in mice. The chimeric approach is applicable for rapid updating of immunogens, and our data supported the use of variant-adapted multivalent vaccine against circulating and emerging variants.


Subject(s)
COVID-19 , Vaccines , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Mice , SARS-CoV-2/genetics
3.
Biochim Biophys Acta Proteins Proteom ; 1870(2): 140736, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1509583

ABSTRACT

We present an integrated analysis of urine and serum proteomics and clinical measurements in asymptomatic, mild/moderate, severe and convalescent cases of COVID-19. We identify the pattern of immune response during COVID-19 infection. The immune response is activated in asymptomatic infection, but is dysregulated in mild and severe COVID-19 patients. Our data suggest that the turning point depends on the function of myeloid cells and neutrophils. In addition, immune defects persist into the recovery stage, until 12 months after diagnosis. Moreover, disorders of cholesterol metabolism span the entire progression of the disease, starting from asymptomatic infection and lasting to recovery. Our data suggest that prolonged dysregulation of the immune response and cholesterol metabolism might be the pivotal causative agent of other potential sequelae. Our study provides a comprehensive understanding of COVID-19 immunopathogenesis, which is instructive for the development of early intervention strategies to ameliorate complex disease sequelae.


Subject(s)
Asymptomatic Infections , COVID-19/immunology , Cholesterol/metabolism , Convalescence , Proteomics , COVID-19/blood , COVID-19/urine , Case-Control Studies , Cholesterol/blood , Enzyme-Linked Immunosorbent Assay , Humans , Immunity , Myeloid Cells/immunology , Neutrophils/immunology , SARS-CoV-2/isolation & purification
4.
Emerg Microbes Infect ; 10(1): 1574-1588, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1320287

ABSTRACT

A safe and effective vaccine is urgently needed to control the unprecedented COVID-19 pandemic. Four adenovirus-vectored vaccines expressing spike (S) protein have been approved for use. Here, we generated several recombinant chimpanzee adenovirus (AdC7) vaccines expressing S, receptor-binding domain (RBD), or tandem-repeat dimeric RBD (RBD-tr2). We found vaccination via either intramuscular or intranasal route was highly immunogenic in mice to elicit both humoral and cellular immune responses. AdC7-RBD-tr2 showed higher antibody responses compared to either AdC7-S or AdC7-RBD. Intranasal administration of AdC7-RBD-tr2 additionally induced mucosal immunity with neutralizing activity in bronchoalveolar lavage fluid. Either single-dose or two-dose mucosal administration of AdC7-RBD-tr2 protected mice against SARS-CoV-2 challenge, with undetectable subgenomic RNA in lung and relieved lung injury. AdC7-RBD-tr2-elicted sera preserved the neutralizing activity against the circulating variants, especially the Delta variant. These results support AdC7-RBD-tr2 as a promising COVID-19 vaccine candidate.


Subject(s)
Adenoviridae/genetics , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , Spike Glycoprotein, Coronavirus/immunology , Administration, Intranasal , Animals , Antibodies, Neutralizing/blood , COVID-19 , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/genetics , Chlorocebus aethiops , Female , Genetic Vectors/genetics , HEK293 Cells , Humans , Immunogenicity, Vaccine , Injections, Intramuscular , Mice , Mice, Inbred BALB C , Pan troglodytes/virology , Protein Binding , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/administration & dosage , Spike Glycoprotein, Coronavirus/genetics , Vaccination , Vero Cells
6.
Front Public Health ; 8: 368, 2020.
Article in English | MEDLINE | ID: covidwho-854041

ABSTRACT

Background: The COVID-19 outbreak, which was first reported in Wuhan, China, in December 2019, began to spread throughout the world, and now involves over 200 countries. Methods: A total of 37 overseas young and middle-aged people, who tested as SARS-CoV-2 positive upon their return to Shanghai, were enrolled for an analysis of their clinical symptoms, blood routine indexes, and lung CT images. Results: The clinical symptoms were characterized by fever (51.4%), dry cough (13.5%), expectoration (27.0%), hypodynamia (21.6%), pharyngalia (10.8%), pharynoxerosis (8.1%), rhinobyon (13.5%), rhinorrhea (8.1%), muscular soreness (16.2%), and diarrhea (2.7%). In 16.2% of cases, no symptoms were reported. Fever was the most common symptom (51.40%). The pneumonic changes referred to the latticed ground glass imaging and similar white lung imaging accompanied by consolidated shadows. The rate of pneumonia was high (81.10%). We found that the exclusive percent of eosinophils was abnormally low. By analyzing the correlation of eosinophils, fever, and pneumonia, we found that the percentage of eosinophils was low in the COVID-19 patients afflicted with fever or pneumonia (P < 0.01). Additionally, pneumonia and fever were negatively correlated with the percentage of eosinophils and eosinophils/neutrophils ratio (P < 0.01, respectively), but not associated with pneumonia severity (P > 0.05). Fever was not correlated with pneumonia (P > 0.05). Conclusion: A low percentage of eosinophils may be considered as a biomarker of pneumonia of COVID-19, but not as a biomarker of pneumonia severity.


Subject(s)
COVID-19/immunology , Eosinophils/cytology , Adult , China/epidemiology , Female , Humans , Leukocyte Count , Male , Middle Aged , Travel , Young Adult
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