Author: Mx

Pioneer in Glycan Profiling Technology Environmentally Regenerative Agriculture
Technology

Diagnostic accuracy of COVID-19 Chest CT images with using Deep Learning methodology

A group from Sejong University, Seoul, etc. has reported on the accuracy of COVID-19 diagnosis in chest CT images with applying Deep Learning.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249450

The neural network using in Deep Learning was composed of 20 stages, and convolution and pooling functions were incorporated. The resolution of the input images were (224 x 224, and the sizes of convolution were (3 x 3）and（5 x 5). The obtained overall accuracy was 99.83%（sensitivity＝0.9286, specificity＝0.99). In the future, it will be accelerate to adopt Deep Learning in diagnostic applications.

Technology

Using SARS-CoV-2 nanoparticles as a vaccine, a broadly neutralizing antibody strong to SARS-CoV-2 variants could be induced 

A group from Scripps Research Institute has reported that a broadly neutralizing antibody strong to SARS-CoV-2 variants could be induced by using SARS-CoV-2 nanoparticles as a vaccine.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010731/

The main stream of the current vaccines is using platforms which deliver the recombinant SARS-CoV-2 spike as an antigen such as mRNA-encapsulated liposomes (e.g., BNT162b2 and mRNA-1273), adenovirus vectors (e.g., ChAdOx1 nCoV-19 [AZD1222], CTII-nCoV, Sputnik V, and Ad26.COV2.S). There vaccines are compatible with B.1.1.7 variant, but a notable loss of efficacy was reported for B.1.351 and P.1 variants. Therefore, it is required to develop vaccines that can elicit a broadly neutralizing antibody (bNAb) response to SARS-CoV-2 variants. For this purpose, those vaccines have to induce long-lived germinal center (GC) reactions to activate precursor B cells, stimulate affinity maturation, and form long-term immune memory.

The SARS-CoV-2 spike protein is a trimer of S1-S2 heterodimers. The S1 subunit contains a receptor-binding domain (RBD) to initiate infection. The S2 subunit consists of a fusion peptide (FP) and heptad repeat regions 1 and 2 (HR1 and HR2). Authors designed an HR2-deleted glycine-capped spike (S2GΔHR2) to increase the spike stability, and assembled those spikes on a nanoparticle platform called SApNP using I3–01v9 60-mers as a linker (S2GΔHR2-10GS-I3-01v9-LD7-PADRE (I3-01v9-L7P)). The I3–01v9-LP7 presents 20 stabilized spikes.

Using S2GΔHR2-10GS-I3-01v9-L7P as a vaccine, a bNAb were induced showing compatible titers for B.1.1.7, B.1.351, and P.1 variants. Compared with the soluble spike, this nanoparticle showed 6-fold longer retention, 4-fold greater presentation on follicular dendritic cell dendrites, and 5-fold higher germinal center reactions in lymph node follicles. The reason of this effect is not clear yet, but would be related to the size effect.

Technology

The effect of Transgenic Expression of Human C-Type Lectin CLEC18A in Aedes aegypti on suppressing Dengu Virus infectivity and proliferation

A group from National Health Research Institutes, Miaoli, Taiwan, etc. has established a transgenic Aedes aegypti line that expresses human CLEC18A, and has confirmed suppression of dengue virus (DENV) infection and proliferation in Aedes aegypti.
https://www.frontiersin.org/articles/10.3389/fimmu.2021.640367/full

A human C-type lectin protein CLEC18A binds to glycoprotein of dengue virus, induces type-I interferon secretion, making CLEC18A one of players in innate immune responses to DENV infection (detailed glycan binding specificity of CLEC18A is not clear, but usually C-type lectins bind to high mannose or Gal/GalNAc). This study suggests a possibility that could suppress the spread of DENV infection and proliferation by using transgenic mosquitoes.

Nature

Immune Memory (CD4+T-cell reaction) in mild COVID-19 patients and Cross-rectivity of CD4+T-cells against SARS-CoV-2 in unexposed donors

A group from National Institute of Immunology, New Delhi, etc. has reported on immune memory (CD4+T-cell reaction) in mild COVID-19 patients and cross-reactivity of CD4+T-cells against SARS-CoV-2 in unexposed donors
https://www.frontiersin.org/articles/10.3389/fimmu.2021.636768/full

In mild COVID-19 patients, it was reported that the immune memory (i.e, CD4+T-cell reactions to SARS-CoV-2) continues for about 5 months (median about 3 months). On the other hand, in SARS-CoV-2 unexposed donors, there was no immune reaction to SARS-CoV-2 spike protein, but the CD4+ T-cells specific to SARS-CoV-2 N protein were observed in 66% of the donors. In SARS-CoV-2 exposed patients, the CD4+ T-cells targeted SARS-CoV-2 spike protein rather than SARS-CoV-2 N protein.
Whether the cross-reactive CD4+ T cells are contributing to suppressing SARS-CoV-2 infection and further less severe outcome needs to be addressed in the prospective cohort before and after COVID-19.

Nature

Proteinuria would be a good Biomarker for the new coronavirus (COVID-19) severity 

A group from Université Côte d’Azur, Nice, etc. has reported that Proteinuria would be a good Biomarker for the new coronavirus (COVID-19) severity.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985082/

Significant proteinuria (>0.3 g/g) was related to
higher prevalence of ICU admission [OR = 4.72, IC95 (1.16–23.21), p = 0.03],
acute respiratory distress syndrome (ARDS) [OR = 6.89, IC95 (1.41–53.01, p = 0.02)],
longer hospital stay [19 days (9–31) versus 7 days (5–11), p = 0.001].

Nature

Cell surface N-glycan of Candida albicans (mannose core) works anti-inflammatory in sepsis

A group from Kyoto University has reported that the cell surface N-glycan (mannose core) of Candida albicans works anti-inflammatory in sepsis.
https://www.nature.com/articles/s42003-021-01870-3

Sepsis was induced by lipopolysaccharide（LPS）in mouse, and it was demonstrated that purified mannoprotein of Candida albicans stratn J-1020 works anti-inflammatory. Injection of the extracted mannoprotein from J-1020 improved survival greatly. It was found that anti-inflammatory cytokine IL-10 was up-regulated by the injection of J-1020 at this time. It was also confirmed that these phenomena were induced by the interaction between mannoprotein of J-1020 and C-type lectin Dectin-2. When Dectin-2 was knocked out, the survival decreased greatly, and J-1012 mannoprotein did not affect IL-10 production. Further, it was suggested the mannose core of Candida albicans N-glycan is recognized by Dectin-2, leading to suppression of the early onset of septic responses.

Technology

Inactivation of the new corona virus (SARS-CoV-2) by UV-C irradiation

A group from University of Milan, etc. has reported on inactivation of SARS-CoV-2 with UV-C irradiation.
https://www.nature.com/articles/s41598-021-85425-w

Authors irradiated UV-C (254nm) on V6 cells with different Multipulicity of Infection (MOI). 0.05 MOI, 5 MOI, and 1000MOI. 0.05 MOI is equivalent to the low-level contamination observed in closed environments, 5 MOI corresponds to the average concentration found in the sputum of COVID-19 infected patients, and 1000 MOI is a very large concentration, corresponding to that observed in terminally diseased COVID-19 patients. In a range from 0.05 MOI to 5 MOI, a very small dose of 4 mJ/cm2 was enough to achieve full inactivation of the virus. Even at the highest value, 1000 MOI, virus was totally inactivated with a dose of 16.9 mJ/cm2.

Nature

The amount of serum IgG in SARS-CoV-2 positive patients is inversely correlated with age at around 20 years old as a boundary

A group from Weill Cornell Medicine, New York has reported on the relationship between serum IgG and Age with using serum samples gathered from April 2020 to June 2020.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2777743

The correlation diagram between serum IgG and Age using 85 SARS-CoV-2 positive pediatric and 3648 positive adult patient samples is shown below. The result is quite interesting. It is clearly found that the amount of serum IgG is inversely correlated with age at around 20 years old as a boundary. It remains unclear why patients aged 19 to 25 years exhibited lower levels of SARS-CoV-2 IgG antibodies than children and older adults.

Nature

Site-specific O-glycan analysis of the new coronavirus (SARS-CoV-2)

A group from University of Copenhagen, etc. has reported on site-specific O-glycan analysis of the new coronavirus (SARS-CoV-2).
https://www.biorxiv.org/content/10.1101/2021.02.03.429627v2

Authors used SARS-CoV-2 Spike proteins expressed in Drosophia and HEK 293 F cells. N-glycans were removed by PNGase F, and then Sialic acids were also removed by neuraminidase. Glycan analysis was done by using ETD/HCD LC-MS/MS. O-glycan modification in HEK 293 F is shown blow. Tn-antigen seems to be more expressed than Tn-antigen. There is no information about sialylation of T- and Tn-antigens.

Nature

O-glycan analysis of the new coronavirus (SARS-CoV-2)

A group from University of Wisconsin-Madison, etc. has reported on the analysis of O-glycans expressed on the new coronavirus (SARS-CoV-2).
https://www.biorxiv.org/content/10.1101/2021.02.28.433291v1

In order to analyze O-glycans, N-glycans on SARS-CoV-2 spike protein expressed with HEK293 were removed by PNGase F treatment. Authors combined ion mobility spectrometry (TIMS) and ultrahigh-resolution Fourier transform ion cyclotron resonance (FTICR) MS analysis.
As a result, it was found that the majority of the O-glycan modification was Sialyl-T-antigen.