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1.
Front Immunol ; 13: 952650, 2022.
Article in English | MEDLINE | ID: covidwho-2326989

ABSTRACT

Given pandemic risks of zoonotic SARS-CoV-2 variants and other SARS-like coronaviruses in the future, it is valuable to perform studies on conserved antigenic sites to design universal SARS-like coronavirus vaccines. By using antibodies obtained from convalescent COVID-19 patients, we succeeded in functional comparison of conserved antigenic sites at multiple aspects with each other, and even with SARS-CoV-2 unique antigenic sites, which promotes the cognition of process of humoral immune response to the conserved antigenic sites. The conserved antigenic sites between SARS-CoV-2 and SARS-CoV can effectively induce affinity maturation of cross-binding antibodies, finally resulting in broadly neutralizing antibodies against multiple variants of concern, which provides an important basis for universal vaccine design, however they are subdominant, putatively due to their lower accessibility relative to SARS-CoV-2 unique antigenic sites. Furthermore, we preliminarily design RBDs to improve the immunogenicity of these conserved antigenic sites. Our study focusing on conserved antigenic sites provides insights for promoting the development of universal SARS-like coronavirus vaccines, thereby enhancing our pandemic preparedness.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Broadly Neutralizing Antibodies , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Spike Glycoprotein, Coronavirus/genetics
2.
J Coll Physicians Surg Pak ; 32(12): 1637-1639, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2269966

ABSTRACT

The objective of the study was to investigate whether the peripheral lymphocyte count was independently negative association with viral clearance time of SARS-CoV-2 in Chinese patients with COVID-19. Total 202 patients were chosen for the last data analysis. The patients' mean age was 41.39±12.47 years. Male was accounted for 48.51% and female was 51.49% respectively. The average viral clearance time was 19.40±9.03 days. Adjusted linear regression result showed peripheral lymphocyte count was associated with viral clearance time negatively after adjusting confounders (ß, -2.79; 95% CI, -5.21 to -0.36). The trend of peripheral lymphocyte count treated as a categorical variable in linear regression was also consistent with the result when peripheral lymphocyte count was treated as a continuous variable. There was a negative association between peripheral lymphocyte count and viral clearance time of SARS-CoV-2 in Chinese patients with COVID-19. Key Words: Peripheral lymphocyte count, Viral clearance, COVID-19.

3.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-2046995

ABSTRACT

Given pandemic risks of zoonotic SARS-CoV-2 variants and other SARS-like coronaviruses in the future, it is valuable to perform studies on conserved antigenic sites to design universal SARS-like coronavirus vaccines. By using antibodies obtained from convalescent COVID-19 patients, we succeeded in functional comparison of conserved antigenic sites at multiple aspects with each other, and even with SARS-CoV-2 unique antigenic sites, which promotes the cognition of process of humoral immune response to the conserved antigenic sites. The conserved antigenic sites between SARS-CoV-2 and SARS-CoV can effectively induce affinity maturation of cross-binding antibodies, finally resulting in broadly neutralizing antibodies against multiple variants of concern, which provides an important basis for universal vaccine design, however they are subdominant, putatively due to their lower accessibility relative to SARS-CoV-2 unique antigenic sites. Furthermore, we preliminarily design RBDs to improve the immunogenicity of these conserved antigenic sites. Our study focusing on conserved antigenic sites provides insights for promoting the development of universal SARS-like coronavirus vaccines, thereby enhancing our pandemic preparedness.

4.
Vaccine ; 40(47): 6839-6848, 2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2042193

ABSTRACT

The ongoing coronavirus disease-19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has drastically changed our way of life and continues to have an unmitigated socioeconomic impact across the globe. Research into potential vaccine design and production is focused on the spike (S) protein of the virus, which is critical for virus entry into host cells. Yet, whether the degree of glycosylation in the S protein is associated with vaccine efficacy remains unclear. Here, we first optimized the expression of the S protein in mammalian cells. While we found no significant discrepancy in purity, homogeneity, or receptor binding ability among S proteins derived from 293F cells (referred to as 293F S-2P), 293S GnTI- cells (defective in N-acetylglucosaminyl transferase I enzyme; 293S S-2P), or TN-5B1-4 insect cells (Bac S-2P), there was significant variation in the glycosylation patterns and thermal stability of the proteins. Compared with the partially glycosylated 293S S-2P or Bac S-2P, the fully glycosylated 293F S-2P exhibited higher binding reactivity to convalescent sera. In addition, 293F S-2P induced higher IgG and neutralizing antibody titres than 293S or Bac S-2P in mice. Furthermore, a prime-boost-boost regimen, using a combined immunization of S-2P proteins with various degrees of glycosylation, elicited a more robust neutralizing antibody response than a single S-2P alone. Collectively, this study provides insight into ways to design a more effective SARS-CoV-2 immunogen.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Humans , Mice , Animals , SARS-CoV-2 , Glycosylation , COVID-19/prevention & control , Antibodies, Neutralizing , Antibodies, Viral , Mammals/metabolism , COVID-19 Serotherapy
5.
Medicine (Baltimore) ; 99(44): e23064, 2020 Oct 30.
Article in English | MEDLINE | ID: covidwho-990918

ABSTRACT

Coronavirus disease 2019 (COVID-19) is the most important global public health issue that we currently face. We aimed to explore the clinical features of patients with COVID-19 and compared them with those of hospitalized community-acquired pneumonia (CAP) patients caused by influenza virus during the same period.From Jan 1, to Mar 4, 2020, patients with COVID-19 or CAP caused by influenza virus who were admitted to the First Affiliated Hospital of Xiamen University were consecutively screened for enrollment.A total of 35 COVID-19 patients and 22 CAP patients caused by influenza virus were included in this study. Most of COVID-19 patients had characteristics of familial clustering (63%), however, in the other group, there was no similar finding. The percentages of patients with a high fever (the highest recorded temperature was ≥39.0°C; 11% vs 45% [COVID-19 vs CAP groups, respectively]), dyspnea (9% vs 59%), leukocytosis (3% vs 32%), elevated C-reactive protein concentrations (>10 mg/L, 48% vs 86%), elevated procalcitonin levels (>0.1 ng/ml, 15% vs 73%), PaO2/FiO2 <200 mm Hg (4% vs 22%), and infiltration on imaging (29% vs 68%) in the COVID-19 group were less than those same indices in the hospitalized CAP patients caused by influenza virus. Ground-glass opacity with reticular pattern (63%) and interlobular septal thickening (71%) in chest CT were commonly observed in the COVID-19 group.COVID-19 and CAP caused by influenza virus appear to share some similarities in clinical manifestaions but they definitely have major distinctions. Influenza infection remains a health problem even during COVID-19 pandemic.


Subject(s)
Coronavirus Infections/epidemiology , Influenza, Human/epidemiology , Pneumonia, Viral/epidemiology , Adult , Aged , Aged, 80 and over , COVID-19 , China/epidemiology , Community-Acquired Infections , Coronavirus Infections/blood , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/drug therapy , Coronavirus Infections/therapy , Cross-Sectional Studies , Female , Humans , Influenza, Human/blood , Influenza, Human/diagnostic imaging , Influenza, Human/therapy , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/therapy , Radiography, Thoracic , Retrospective Studies , COVID-19 Drug Treatment
6.
Emerg Microbes Infect ; 9(1): 2076-2090, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-913103

ABSTRACT

The current coronavirus disease 2019 (COVID-19) pandemic was the result of the rapid transmission of a highly pathogenic coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there is no efficacious vaccine or therapeutic. Toward the development of a vaccine, here we expressed and evaluated as potential candidates four versions of the spike (S) protein using an insect cell expression system: receptor binding domain (RBD), S1 subunit, the wild-type S ectodomain (S-WT), and the prefusion trimer-stabilized form (S-2P). We showed that RBD appears as a monomer in solution, whereas S1, S-WT, and S-2P associate as homotrimers with substantial glycosylation. Cryo-electron microscopy analyses suggested that S-2P assumes an identical trimer conformation as the similarly engineered S protein expressed in 293 mammalian cells but with reduced glycosylation. Overall, the four proteins confer excellent antigenicity with convalescent COVID-19 patient sera in enzyme-linked immunosorbent assay (ELISA), yet show distinct reactivities in immunoblotting. RBD, S-WT and S-2P, but not S1, induce high neutralization titres (>3-log) in mice after a three-round immunization regimen. The high immunogenicity of S-2P could be maintained at the lowest dose (1 µg) with the inclusion of an aluminium adjuvant. Higher doses (20 µg) of S-2P can elicit high neutralization titres in non-human primates that exceed 40-times the mean titres measured in convalescent COVID-19 subjects. Our results suggest that the prefusion trimer-stabilized SARS-CoV-2 S-protein from insect cells may offer a potential candidate strategy for the development of a recombinant COVID-19 vaccine.


Subject(s)
Antigens, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Immunogenicity, Vaccine/immunology , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Spike Glycoprotein, Coronavirus/immunology , Viral Vaccines/immunology , Angiotensin-Converting Enzyme 2 , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19 , COVID-19 Vaccines , Cell Line , Coronavirus Infections/immunology , Cryoelectron Microscopy , Enzyme-Linked Immunosorbent Assay , Humans , Macaca fascicularis , Mice , Mice, Inbred BALB C , Neutralization Tests , Peptidyl-Dipeptidase A/metabolism , Protein Domains/genetics , Protein Domains/immunology , SARS-CoV-2 , Sf9 Cells , Spike Glycoprotein, Coronavirus/genetics , Spodoptera , Vaccination , Viral Envelope Proteins/immunology
7.
The European respiratory journal ; 2020.
Article | WHO COVID | ID: covidwho-324353

ABSTRACT

BACKGROUND: Timely diagnosis of SARS-CoV-2 infection is a prerequisite for treatment and prevention. The serology characteristics and complement diagnosis value of the antibody test to RNA test need to be demonstrated. METHOD: Serial sera of 80 patients with PCR-confirmed COVID-19 were collected at the First Affiliated Hospital of Zhejiang University, China. Total antibody (Ab), IgM and IgG antibodies against SARS-CoV-2 were detected, and the antibody dynamics during the infection were described. RESULTS: The seroconversion rates for Ab, IgM and IgG were 98.8%, 93.8% and 93.8%, respectively. The first detectible serology marker was Ab, followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 days post exposure (d.p.e) or 9, 10 and 12 days post onset (d.p.o), respectively. The antibody levels increased rapidly beginning at 6 d.p.o. and were accompanied by a decline in viral load. For patients in the early stage of illness (0-7 d.p.o), Ab showed the highest sensitivity (64.1%) compared to IgM and IgG (33.3% for both, p<0.001). The sensitivities of Ab, IgM and IgG increased to 100%, 96.7% and 93.3% 2 weeks later, respectively. When the same antibody type was detected, no significant difference was observed between enzyme-linked immunosorbent assays and other forms of immunoassays. CONCLUSIONS: A typical acute antibody response is induced during SARS-CoV-2 infection. Serology testing provides an important complement to RNA testing in the later stages of illness for pathogenic specific diagnosis and helpful information to evaluate the adapted immunity status of patients.

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