Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
1.
Diagnostics (Basel) ; 12(7)2022 Jul 10.
Article in English | MEDLINE | ID: covidwho-1928517

ABSTRACT

Although the fibrinogen-to-albumin ratio (F/R ratio) has been used as an inflammation marker to predict clinical outcomes in patients with cardiovascular diseases, its association with the prognosis of patients with coronavirus disease 2019 (COVID-19) remains unclear. Electronic databases including EMBASE, MEDLINE, Google Scholar, and Cochrane Library were searched from inception to 20 June 2022. The associations of F/R ratio with poor prognosis (defined as the occurrence of mortality or severe disease) were investigated in patients with COVID-19. A total of 10 studies (seven from Turkey, two from China, one from Croatia) involving 3675 patients published between 2020 and 2022 were eligible for quantitative syntheses. Merged results revealed a higher F/R ratio in the poor prognosis group (standardized mean difference: 0.529, p < 0.001, I2 = 84.8%, eight studies) than that in the good prognosis group. In addition, a high F/R ratio was associated with an increased risk of poor prognosis (odds ratio: 2.684, I2 = 59.5%, five studies). Pooled analysis showed a sensitivity of 0.75, specificity of 0.66, and area under curve of 0.77 for poor prognosis prediction. In conclusion, this meta-analysis revealed a positive correlation between F/A ratio and poor prognostic outcomes of COVID-19. Because of the limited number of studies included, further investigations are warranted to support our findings.

2.
Sci Transl Med ; 14(639): eabm0899, 2022 04 06.
Article in English | MEDLINE | ID: covidwho-1714341

ABSTRACT

A major challenge to end the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is to develop a broadly protective vaccine that elicits long-term immunity. As the key immunogen, the viral surface spike (S) protein is frequently mutated, and conserved epitopes are shielded by glycans. Here, we revealed that S protein glycosylation has site-differential effects on viral infectivity. We found that S protein generated by lung epithelial cells has glycoforms associated with increased infectivity. Compared to the fully glycosylated S protein, immunization of S protein with N-glycans trimmed to the mono-GlcNAc-decorated state (SMG) elicited stronger immune responses and better protection for human angiotensin-converting enzyme 2 (hACE2) transgenic mice against variants of concern (VOCs). In addition, a broadly neutralizing monoclonal antibody was identified from SMG-immunized mice that could neutralize wild-type SARS-CoV-2 and VOCs with subpicomolar potency. Together, these results demonstrate that removal of glycan shields to better expose the conserved sequences has the potential to be an effective and simple approach for developing a broadly protective SARS-CoV-2 vaccine.


Subject(s)
COVID-19 Vaccines , Polysaccharides , Spike Glycoprotein, Coronavirus , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/immunology , COVID-19 Vaccines/metabolism , Humans , Mice , Models, Animal , SARS-CoV-2 , Vaccination
3.
Proc Natl Acad Sci U S A ; 119(9)2022 03 01.
Article in English | MEDLINE | ID: covidwho-1684242

ABSTRACT

Development of the messenger RNA (mRNA) vaccine has emerged as an effective and speedy strategy to control the spread of new pathogens. After vaccination, the mRNA is translated into the real protein vaccine, and there is no need to manufacture the protein in vitro. However, the fate of mRNA and its posttranslational modification inside the cell may affect immune response. Here, we showed that the mRNA vaccine of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein with deletion of glycosites in the receptor-binding domain (RBD) or especially the subunit 2 (S2) domain to expose more conserved epitopes elicited stronger antibody and CD8+ T cell responses with broader protection against the alpha, beta, gamma, delta, and omicron variants, compared to the unmodified mRNA. Immunization of such mRNA resulted in accumulation of misfolded spike protein in the endoplasmic reticulum, causing the up-regulation of BiP/GRP78, XBP1, and p-eIF2α to induce cell apoptosis and strong CD8+ T cell response. In addition, dendritic cells (DCs) incubated with S2-glysosite deleted mRNA vaccine increased class I major histocompatibility complex (MHC I) expression. This study provides a direction for the development of broad-spectrum mRNA vaccines which may not be achieved with the use of expressed proteins as antigens.


Subject(s)
COVID-19 Vaccines/immunology , Spike Glycoprotein, Coronavirus/genetics , Animals , Antibodies, Viral/immunology , Antibody Formation , CD8-Positive T-Lymphocytes/immunology , Cytokines/metabolism , Glycosylation , HEK293 Cells , Histocompatibility Antigens/metabolism , Humans , Immunity , Mice, Inbred BALB C , Unfolded Protein Response , Vaccines, Synthetic/immunology , /immunology
4.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-294970

ABSTRACT

A major challenge to end the pandemic caused by SARS-CoV-2 is to develop a broadly protective vaccine. As the key immunogen, the spike protein is frequently mutated with conserved epitopes shielded by glycans. Here, we reveal that spike glycosylation has site-differential effects on viral infectivity and lung epithelial cells generate spike with more infective glycoforms. Compared to the fully glycosylated spike, immunization of spike protein with N-glycans trimmed to the monoglycosylated state (S mg ) elicits stronger immune responses and better protection for hACE2 transgenic mice against variants of concern. In addition, a broadly neutralizing monoclonal antibody was identified from the S mg immunized mice, demonstrating that removal of glycan shields to better expose the conserved sequences is an effective and simple approach to broad-spectrum vaccine development. One-Sentence Summary Removing glycan shields to expose conserved epitopes is an effective approach to develop a broad-spectrum SARS-CoV-2 vaccine.

5.
PLoS Pathog ; 17(3): e1009407, 2021 03.
Article in English | MEDLINE | ID: covidwho-1338134

ABSTRACT

Incessant antigenic evolution enables the persistence and spread of influenza virus in the human population. As the principal target of the immune response, the hemagglutinin (HA) surface antigen on influenza viruses continuously acquires and replaces N-linked glycosylation sites to shield immunogenic protein epitopes using host-derived glycans. Anti-glycan antibodies, such as 2G12, target the HIV-1 envelope protein (Env), which is even more extensively glycosylated and contains under-processed oligomannose-type clusters on its dense glycan shield. Here, we illustrate that 2G12 can also neutralize human seasonal influenza A H3N2 viruses that have evolved to present similar oligomannose-type clusters on their HAs from around 20 years after the 1968 pandemic. Using structural biology and mass spectrometric approaches, we find that two N-glycosylation sites close to the receptor binding site (RBS) on influenza hemagglutinin represent the oligomannose cluster recognized by 2G12. One of these glycan sites is highly conserved in all human H3N2 strains and the other emerged during virus evolution. These two N-glycosylation sites have also become crucial for fitness of recent H3N2 strains. These findings shed light on the evolution of the glycan shield on influenza virus and suggest 2G12-like antibodies can potentially act as broad neutralizers to target human enveloped viruses.


Subject(s)
Antibodies, Viral/immunology , HIV-1/immunology , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Influenza A Virus, H3N2 Subtype/immunology , Broadly Neutralizing Antibodies , Cross Reactions , HIV Infections/immunology , Humans , Influenza, Human/immunology
6.
Cell Rep ; 32(6): 108016, 2020 08 11.
Article in English | MEDLINE | ID: covidwho-670926

ABSTRACT

The influenza virus hemagglutinin (HA) and coronavirus spike (S) protein mediate virus entry. HA and S proteins are heavily glycosylated, making them potential targets for carbohydrate binding agents such as lectins. Here, we show that the lectin FRIL, isolated from hyacinth beans (Lablab purpureus), has anti-influenza and anti-SARS-CoV-2 activity. FRIL can neutralize 11 representative human and avian influenza strains at low nanomolar concentrations, and intranasal administration of FRIL is protective against lethal H1N1 infection in mice. FRIL binds preferentially to complex-type N-glycans and neutralizes viruses that possess complex-type N-glycans on their envelopes. As a homotetramer, FRIL is capable of aggregating influenza particles through multivalent binding and trapping influenza virions in cytoplasmic late endosomes, preventing their nuclear entry. Remarkably, FRIL also effectively neutralizes SARS-CoV-2, preventing viral protein production and cytopathic effect in host cells. These findings suggest a potential application of FRIL for the prevention and/or treatment of influenza and COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Fabaceae/chemistry , Orthomyxoviridae Infections/drug therapy , Plant Lectins/therapeutic use , Pneumonia, Viral/drug therapy , A549 Cells , Administration, Intranasal , Animals , Antiviral Agents/administration & dosage , Antiviral Agents/pharmacology , Betacoronavirus/drug effects , COVID-19 , Chick Embryo , Chlorocebus aethiops , Dogs , Female , Humans , Influenza A Virus, H1N1 Subtype/drug effects , Madin Darby Canine Kidney Cells , Mice , Mice, Inbred BALB C , Pandemics , Plant Lectins/administration & dosage , Plant Lectins/pharmacology , Protein Binding , SARS-CoV-2 , Vero Cells , Viral Envelope Proteins/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL