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1.
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
2.
Medicine (Baltimore) ; 101(2): e28600, 2022 Jan 14.
Article in English | MEDLINE | ID: covidwho-1722696

ABSTRACT

BACKGROUND: From the end of 2019 to now, coronavirus disease 2019 (COVID-19) has put enormous strain on the world's health systems, causing significant deaths and economic losses worldwide. Nasal congestion, one of the symptoms of COVID-19, poses considerable problems for patients. In China, acupuncture has been widely used to treat nasal congestion caused by COVID-19, but there is still a lack of evidence-based medical evaluation. METHODS: According to the retrieval strategies, randomized controlled trials on the acupuncture for COVID-19 nasal congestion were obtained from China National Knowledge Infrastructure, WanFang, VIP, PubMed, Embase, and Cochrane Library, regardless of publication date, or language. Studies were screened based on inclusion and exclusion criteria, and the Cochrane risk bias assessment tool was used to evaluate the quality of the studies. The meta-analysis was performed using Review Manager (RevMan 5.3) and STATA 14.2 software. Ultimately, the evidentiary grade for the results will be evaluated. RESULTS: The study will provide a high-quality and convincing assessment of the efficacy and safety of acupuncture in the treatment of COVID-19's nasal congestion and will be published in peer-reviewed journals. CONCLUSION: Our findings will provide references for future clinical decision and guidance development. PROSPERO REGISTRATION NUMBER: NO.CRD42021299482.


Subject(s)
Acupuncture Therapy , COVID-19/complications , Nose Diseases/therapy , Humans , Meta-Analysis as Topic , Nose Diseases/complications , Research Design , SARS-CoV-2 , Systematic Reviews as Topic , Treatment Outcome
3.
Nat Commun ; 12(1): 5652, 2021 09 27.
Article in English | MEDLINE | ID: covidwho-1440473

ABSTRACT

The emergence of numerous variants of SARS-CoV-2, the causative agent of COVID-19, has presented new challenges to the global efforts to control the COVID-19 pandemic. Here, we obtain two cross-neutralizing antibodies (7D6 and 6D6) that target Sarbecoviruses' receptor-binding domain (RBD) with sub-picomolar affinities and potently neutralize authentic SARS-CoV-2. Crystal structures show that both antibodies bind a cryptic site different from that recognized by existing antibodies and highly conserved across Sarbecovirus isolates. Binding of these two antibodies to the RBD clashes with the adjacent N-terminal domain and disrupts the viral spike. Both antibodies confer good resistance to mutations in the currently circulating SARS-CoV-2 variants. Thus, our results have direct relevance to public health as options for passive antibody therapeutics and even active prophylactics. They can also inform the design of pan-sarbecovirus vaccines.


Subject(s)
Antibodies, Viral/immunology , Broadly Neutralizing Antibodies/immunology , COVID-19/therapy , Immunization, Passive/methods , SARS-CoV-2/immunology , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/isolation & purification , Antibodies, Monoclonal/metabolism , Antibodies, Viral/administration & dosage , Antibodies, Viral/isolation & purification , Antibodies, Viral/metabolism , Binding Sites/genetics , Binding Sites/immunology , Broadly Neutralizing Antibodies/administration & dosage , Broadly Neutralizing Antibodies/isolation & purification , Broadly Neutralizing Antibodies/metabolism , CHO Cells , COVID-19/epidemiology , COVID-19/immunology , COVID-19/virology , Chlorocebus aethiops , Cricetulus , Epitopes/immunology , HEK293 Cells , Humans , Mice , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/immunology , Neutralization Tests , Pandemics/prevention & control , Protein Multimerization , Receptors, Virus/metabolism , SARS-CoV-2/genetics , Sf9 Cells , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells
4.
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
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