Products & solutions & information collection of COVID-19 vaccines, new variants of SARS-CoV-2 and efficacy evaluation solutions

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Table of Contents

BACKGROUND

Challenge of COVID-19 vaccine discovery & development: to meet accumulated mutating of SARS-CoV-2 and a long-term viral genome transcrption

COVID-19 (Coronavirus Disease 2019) is novel viral pneumonia caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, also called 2019nCoV). The world is in midst of the COVID-19 pandemic. Effective vaccines are needed to halt the spread of the SARS-CoV-2 pandemic. Based on the data from WTO, there are 52 COVID-19 vaccines in clinical stage (Supplementary Table 1.) and 162 COVID-19 vaccine candidates in pre-clinical stage (Supplementary Table 2.) 2 mRNA vaccines, the BNT162b2 from Pfizer&BioNTech and the mRNA-1273 from Moderna, have recently been issued the emergency use authorization (EUA) by the U.S. Food and Drug Administration (FDA) for the prevention of COVID-19 in individuals 16 years of age and older.

The efficacy and safety of COVID-19 vaccine candidates need carefully investigated, from pre-clinical, clinal stage to a long time after BLA. There are 2 important items here:

Firstly, the coronavirus is kept accumulated mutating. The most important mutation occurs in SARS-CoV-2 (2019nCoV) Spike protein (SARS-CoV-2 S protein). The SARS-CoV-2 (2019nCoV) Spike mediates binding and entry into host cells and is a major target of neutralizing antibodies. Most of the COVID-19 vaccines focus on spike protein1,4-6.

Different SARS-CoV-2 lineages with diverse Spike protein mutant variants may yield a heavy impact on the course of the pandemic2-3. The United Kingdom (UK) has faced a rapid increase in COVID-19 cases caused by a novel SARS-COV-2 (2019nCOV) lineage, the B.1.1.7 lineage, which carries a larger than a usual number of coronavirus genetic changes7-8, particularly in the SARS-CoV-2 spike protein(Table 1)7.
Gene Nucleotide Amino acid
ORF1ab C3267T T1001I
C5388A A1708D
T6954C I2230T
11288-11296 deletion SGF 3675-3677 deletion
spike 21765-21770 deletion HV 69-70 deletion (Click to more details about HV 69-70 deletion related products)
21991-21993 deletion Y144 deletion
A23063T N501Y (Click to more details about N501Y related products)
C23271A A570D
C23604A P681H
C23709T T716I
T24506G S982A
G24914C D1118H
Orf8 C27972T Q27stop
G28048T R52I
A28111G Y73C
N 28280 GAT->CTA D3L
C28977T S235F

Secondly, SARS-CoV-2 was reported to integrate into the genome, which means a stable long-term expression of transcript products of SARS-CoV-2 9.

In conclusion, the Efficacy of COVID-19 vaccines and neutralized antibodies need long-term tracking, which mainly focuses on the novel spike protein mutation occurring in the new lineage variant of SARS-CoV2. The efficacy evaluation solution and tools of COVID-19 vaccines and neutralized antibodies need continually updated.

PRODUCTS & PROCOTOL COLLECTION

GeneMedi Efficacy Assay/Evaluation Solutions for COVID-19 Vaccines and Therapeutic antibodies against SARS-CoV2(2019nCoV)

To meet accumulated mutating of SARS-CoV-2, GeneMedi keeps continually developing novel solutions and tools for efficacy evaluation of COVID-19 vaccines (and neutralized antibodies) against novel mutant SARS-CoV-2 (2019nCoV) lineages. Our scientist’s team takes duty in fighting against the COVID-19 pandemic with our global industrial and academic partners.

GeneMedi information and products collection of SARS-COV-2 (2019nCOV) UK B.1.1.7 lineage and South Africa 501Y.V2 lineage and Brazilian P.1 lineage(B.1.1.28.1)

GeneMedi pseudotyped virus (pseudovirus) of SARS-COV-2 (2019nCOV) B.1.1.7 lineage

Taking responsibility to help accelerate the COVID-19 vaccine and therapeutic antibody discovery and development, GeneMedi had developed the pseudotype virus (pseudovirus) of SARS-COV-2 (2019nCOV) B.1.1.7 lineage, which will meet the evaluation of the efficacy of COVID19 vaccines and therapeutic antibodies.

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GeneMedi pseudotyped virus (pseudovirus) of SARS-COV-2 (2019nCOV) 501Y.V2 lineage

Taking responsibility to help accelerate the COVID-19 vaccine and therapeutic antibody discovery and development, GeneMedi had developed the pseudotype virus (pseudovirus) of SARS-COV-2 (2019nCOV) S501Y.V2 lineage, which will meet the evaluation of the efficacy of COVID19 vaccines and therapeutic antibodies.

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GeneMedi pseudotype virus (pseudovirus) of SARS-COV-2 (2019nCOV) P.1 lineage(B.1.1.28.1, Brazilian variant)

Taking responsibility to help accelerate the COVID-19 vaccine and therapeutic antibody discovery and development, GeneMedi had developed the pseudotype virus (pseudovirus) of SARS-COV-2 (2019nCOV) P.1 lineage(B.1.1.28.1, Brazilian variant), which will meet the evaluation of the efficacy of COVID19 vaccines and therapeutic antibodies.

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SARS-COV-2 (2019nCOV) B.1.1.7 lineage & 501Y.V2 lineage(B.1.351) & P.1 lineage (B.1.1.28.1, Brazilian variant) of Spike protein & ACE2 competition binding assay for efficacy evaluation of COVID-19 vaccines and therapeutic antibodies

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GeneMedi codon-optimized spike mammalian expression vector for SARS-COV-2 (2019nCOV) B.1.1.7 lineage

GeneMedi designed a mammalian expression codon-optimized spike mutation/deletion variant vector for COVID-19 SARS-COV-2 (2019nCOV) B.1.1.7 lineage.

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pcDNA3.1(+)
No tag

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pcDNA3.1(+)
No tag

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pcDNA3.1(+)
No tag

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Pre-made adenovirus
C-3FLAG
coden optimized for mamamlian

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Pre-made adenovirus
C-3FLAG
coden optimized for mamamlian

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Pre-made adenovirus
C-3FLAG
coden optimized for mamamlian

GeneMedi codon-optimized spike mammalian expression vector for SARS-COV-2 (2019nCOV) South Africa 501Y.V2 lineage(B.1.351).

GeneMedi designed a mammalian expression codon-optimized spike mutation/deletion variant vector for COVID-19 SARS-COV-2 (2019nCOV) S501Y.V2 lineage.

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pcDNA3.1(+)
No tag
coden optimized for mamamlian

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pcDNA3.1(+)
No tag

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pcDNA3.1(+)
No tag
coden optimized for mamamlian

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pcDNA3.1(+)
No tag
coden optimized for mamamlian

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Pre-made adenovirus
C-3FLAG
coden optimized for mamamlian

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Pre-made adenovirus
C-3FLAG
coden optimized for mamamlian

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Pre-made adenovirus
C-3FLAG
coden optimized for mamamlian

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Pre-made adenovirus
C-3FLAG
coden optimized for mamamlian

GeneMedi codon-optimized spike mammalian expression vector for SARS-COV-2 (2019nCOV) - P.1 lineage(B.1.1.28.1, Brazilian variant)

GeneMedi designed a mammalian expression codon-optimized spike mutation/deletion variant vector for COVID-19 SARS-COV-2 (2019nCOV) P.1 lineage(B.1.1.28.1, Brazilian variant)

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pcDNA3.1(+)
No tag
coden optimized for mamamlian

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pcDNA3.1(+)
No tag

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pcDNA3.1(+)
No tag
coden optimized for mamamlian

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pcDNA3.1(+)
No tag
coden optimized for mamamlian

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Pre-made adenovirus
C-3FLAG
coden optimized for mamamlian

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Pre-made adenovirus
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coden optimized for mamamlian

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Multiple variants of Spike protein & ACE2 competition binding assay for efficacy evaluation of COVID-19 vaccines and therapeutic antibodies

The Spike proteins variants that GeneMedi offer is including:

1) Multiple variants of recombinant Spike protein for Spike protein & ACE2 competition binding assay for efficacy evaluation of COVID-19 vaccines and therapeutic antibodies

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Cat No.
Products Name
Source (Expression Host)
Tag
Bioactivity validation
Order
Recombinant 2019-nCoV(SARS-CoV-2) Spike Protein RBD mutant (Omicron variant aka B.1.1.529)
Mamamlian (human cell)
C-His
ACE2 binding; Immunogen in Sandwich Elisa, lateral-flow tests,and other immunoassays;
1 3 4

2) Recombinant human ACE2 protein products

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Cat No.
Antigen Name of 2019-nCoV(SARS-CoV-2)
Isotypes
Order
Recombinant human soluble ACE2 protein (soluble hACE2,extracellular hACE2,C-His)
Mamamlian (human cell)
Recombinant human soluble ACE2 protein (soluble hACE2,extracellular hACE2,C-FC)
Mamamlian (human cell)

– Competition assay for neutralizing antibodies, peptides inhibitor and vaccines-immunized serums

Binding activity sbd001
Figure. Immobilized 2019-nCoV S Protein RBD-C-His (GMP-V-2019nCoV-SRBD001) can bind 10μg/ml of Human ACE-2-Fc (GMP-H-ACE2002)

Multi-VariantsTM SARS-CoV2 (wildtype, D614G, N501Y, E484K, B.1.1.7 lineage, 501Y.V2 lineage, and so on) Pseudotype virus-Based Neutralization Assay System for efficacy evaluation of COVID-19 vaccines and therapeutic antibodies (Lentiviral pseudovirus)

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Cat No.
Description
Order
Spike (S1+S2) RBD triple mutation(K417T, E484K and N501Y)+D614G of SARS-CoV-2(2019nCoV) Pseudotyped virus (Brazilian P.1 lineage)
Spike whole mutant SARS-CoV-2(2019nCoV) Brazilian P.1 lineage Pseudotyped virus
Spike(S1+S2) RBD-S477N mutation of SARS-CoV-2(2019nCoV) Pseudotyped virus (B.1.526 lineage; 20A.EU2 lineage) and Pseudovirus Based Neutralization Assay
Spike (S1+S2) RBD mutation (S477N)+ D253G of SARS-CoV-2(2019nCoV) Pseudotyped virus (B.1.526 lineage) production and Pseudovirus Based Neutralization Assay
Spike (S1+S2) RBD mutation (E484K)+ D253G of SARS-CoV-2(2019nCoV) Pseudotyped virus (B.1.526 lineage) production and Pseudovirus Based Neutralization Assay
Spike whole mutant SARS-CoV-2(2019nCoV) B.1.526 lineage Pseudotyped virus production and Pseudovirus Based Neutralization Assay
Spike(S1+S2) RBD-E484Q mutation of SARS-CoV-2(2019nCoV) Pseudotyped virus (double mutant variant EPI_ISL_1360318, S:E484Q+L452R (India)) and Pseudovirus Based Neutralization Assay
Spike (S1+S2) RBD mutation L452R of SARS-CoV-2(2019nCoV) Pseudotyped virus (double mutant variant EPI_ISL_1360318, S:E484Q+L452R (India)) production and Pseudovirus Based Neutralization Assay
Spike (S1+S2) RBD mutation (E484Q+L452R) of SARS-CoV-2(2019nCoV) Pseudotyped virus (double mutant variant EPI_ISL_1360318, S:E484Q+L452R (India)) production and Pseudovirus Based Neutralization Assay
Spike whole mutant SARS-CoV-2(2019nCoV) double mutant variant EPI_ISL_1360318, S:E484Q+L452R (India) Pseudotyped virus production and Pseudovirus Based Neutralization Assay
1 2 3 4

GeneMedi SARS-CoV-2 Pseudovirus (PSV) Based Cell Entry

GeneMedi SARS-CoV-2 Pseudovirus (PSV) Based Cell Entry

Figure. GeneMedi-SARS-CoV-2 Pseudovirus (PSV) Based Cell Entry validation with fluorescence(A), Luciferase activity (B) and FACS (C) after 72 hours of HEK293T infection. hACE2 significantly enhanced the infection efficiency of the SARS-CoV-2 PSV.

GeneMedi SARS-CoV-2 PSV-Luciferase (Cat.GM-2019nCoV-PSV01) is recombinant pseudotyped lentiviral particles containing SARS-CoV-2 spike protein to mimic SARS-CoV-2 (2019nCoV) cell infection.

GM-2019nCoV-PSV01 is a powerful tool for SARS-CoV-2 related vaccine efficacy evaluation, neutralizing antibodies, peptides blockers competitors neutralization assay, and tissue-specific infection determination.
GeneMedi-SARS-CoV-2 WT and Spike Mutation Variants Pseudovirus (PSV) Based Cell Entry
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Figure. The Pseudovirus (PSV) Based Cell Entry assay was performed on 293T-hACE2 cells infected with GeneMedi-SARS-CoV-2 WT and Spike Mutation Variants (D614G, S943P, V367F, G476S, V483A, H49Y, Q239K, A831V, P1263L, D839Y/N/E:D839Y, D839N, D839E) Pseudovirus (PSV) Infection rate was determined by RFP+GFP+/GFP+ with FACS validation.

Codon-optimized mammalian expression vector for SARS-COV-2 (2019nCOV) spike wide type & mutant variants (D614G, N501Y, E484K, B.1.1.7 lineage, 501Y.V2 lineage, and so on)

Codon-optimized viral particle (Adenovirus, Lentivirus, AAV) for SARS-COV-2 (2019nCOV) spike wide type & mutant variants (D614G, N501Y, E484K, B.1.1.7 lineage, 501Y.V2 lineage, and so on)

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Description
Vector
Reporter
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pGMLV-2019nCoV-spike(S1+S2,C-6His)
Lentiviral vector
Zsgreen
pGMLV-2019nCoV-S1(C-6His)
Lentiviral vector
Zsgreen
pGMLV-2019nCoV-Spike RBD(C-6His)
Lentiviral vector
Zsgreen
pGMAAV-2019nCoV-Spike RBD(C-3FLAG)
AAV vector
Zsgreen
pGMLV-2019nCoV-spike£¨S1+S2,C-6His£©
Lentiviral vector
Zsgreen
Ad-2019nCoV-Spike(S1+S2,C-3FLAG)
Pre-made adenovirus
EGFP
Ad-2019nCoV-Spike(S1 protein,C-3FLAG)
Pre-made adenovirus
EGFP
Ad-2019nCoV-Spike(S protein RBD,C-3FLAG)
Pre-made adenovirus
EGFP
Ad-2019nCoV-Spike(S1+S2,C-3FLAG)
Pre-made adenovirus
null
Ad-2019nCoV-Spike D614G (S protein,S1+S2,D614G)
Pre-made adenovirus
null
1 2

293T-ACE2 stable cell line & human ACE2 expression vectors: Effector cell of pseudotype virus-Based Neutralization Assay System for efficacy evaluation of COVID-19 vaccines and therapeutic antibodies (Lentiviral pseudovirus)

Human ACE2 overexpression stable HEK293T cell lines. Catalot Number: GM-SC-293T-hACE2-01 Click here for details
Validation of hACE2 overexpression stable HEK293T cell lines (Cat. GM-SC-293T‐hACE2-01)
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Figure. ACE2 mRNA level Validation in hACE2 overexpression stable HEK293T cell lines: Cat. GM‐SC‐293T‐hACE2‐01 (A) and the cell lines were tested as Mycoplasma free (B).

Products list: Human ACE2 overexpression stable HEK293T cell lines
Cat No. 2019 nCoV related Gene Gene &Vector description of 2019 nCoV Vector Reporter Tag codon Optimized Order
GMV-V-2019nCoV-041 ACE2 pGMLV-hACE2(C-3FLAG) Lentiviral vector Zsgreen C-3FLAG No Picture loading failed.
GMV-V-2019nCoV-042 ACE2 pAD-hACE2(C-3FLAG) Pre-made Adenovirus EGFP C-3FLAG No Picture loading failed.
GMV-V-2019nCoV-043 ACE2 pAD-mACE2(C-3FLAG) Pre-made Adenovirus EGFP C-3FLAG No Picture loading failed.
GMV-V-2019nCoV-044 ACE2 pGMLV-mACE2(C-3FLAG) Lentiviral vector Zsgreen C-3FLAG No Picture loading failed.

Validated SARS-CoV-2 neutralizing antibodies-benchmark COVID-19 neutralizing antibodies.

Cat No. Antigen Name of 2019-nCoV(SARS-CoV-2) Source (Expression Host) Isotypes Bioactivity validation Order
GMP-V-2019nCoV-SnAb001 Anti-2019-nCoV Spike (Spike RBD domain) human monoclonal neutralizing antibody (IgG1) Mammalian (human cell) human IgG1 Validated in COVID-19 Spike protein and Spike-RBD protein binding affnity. COVID-19 related neutralizing potency is validated by 1.2019nCoV pseudotyped virus based neutralization assay in 293T-ACE2 effector cell. 2. competitively blocking the binding of ACE-2 receptor with SARS-CoV-2 Spike protein. Picture loading failed.
GMP-V-2019nCoV-SnAb002 Anti-2019-nCoV Spike (Spike RBD domain) human monoclonal neutralizing antibody (IgM) Mammalian (human cell) human IgM Validated in COVID-19 Spike protein and Spike-RBD protein binding affnity. COVID-19 related neutralizing potency is validated by 1.2019nCoV pseudotyped virus based neutralization assay in 293T-ACE2 effector cell. 2. competitively blocking the binding of ACE-2 receptor with SARS-CoV-2 Spike protein. Picture loading failed.
GMP-V-2019nCoV-SnAb003 Anti-2019-nCoV Spike (Spike RBD domain) human monoclonal neutralizing antibody (IgA) Mammalian (human cell) human IgA Validated in COVID-19 Spike protein and Spike-RBD protein binding affnity. COVID-19 related neutralizing potency is validated by 1.2019nCoV pseudotyped virus based neutralization assay in 293T-ACE2 effector cell. 2. competitively blocking the binding of ACE-2 receptor with SARS-CoV-2 Spike protein. Picture loading failed.
GMP-V-2019nCoV-SnAb004 Anti-2019-nCoV Spike (Spike RBD domain) mouse monoclonal neutralizing antibody (IgG1) Mammalian (human cell) mouse IgG1 Validated in COVID-19 Spike protein and Spike-RBD protein binding affnity. COVID-19 related neutralizing potency is validated by 1.2019nCoV pseudotyped virus based neutralization assay in 293T-ACE2 effector cell. 2. competitively blocking the binding of ACE-2 receptor with SARS-CoV-2 Spike protein. Picture loading failed.
GMP-V-2019nCoV-SnAb005 Anti-2019-nCoV Spike (Spike RBD domain) Cynomolgus monoclonal neutralizing antibody (IgG1) Mammalian (human cell) Cynomolgus (Non human primate, NHP) IgG1 Validated in COVID-19 Spike protein and Spike-RBD protein binding affnity. COVID-19 related neutralizing potency is validated by 1.2019nCoV pseudotyped virus based neutralization assay in 293T-ACE2 effector cell. 2. competitively blocking the binding of ACE-2 receptor with SARS-CoV-2 Spike protein. Picture loading failed.
GeneMedi-SARS-CoV-2 WT and Spike Mutation Variants Pseudovirus (PSV) Based Neutralizing 
Assay with GeneMedi’s anti-2019-nCoV Spike Neutralizing antibodies (Nabs)
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Figure. The Pseudovirus (PSV) Based Neutralizing Assay was performed on 293T-hACE2 cells infected with GeneMedi-SARS-CoV-2 WT and Spike Mutation Variants (D614G, S943P, V367F, G476S, V483A, H49Y, Q239K, A831V, P1263L, D839Y/N/E:D839Y, D839N, D839E) Pseudovirus (PSV) under treatment of GeneMedi’s anti-2019-nCoV Spike Neutralizing antibodies (Nabs) . Inhibition rate was determined by comparing the relative RFP+GFP+/GFP+ rate.

GeneMedi’s anti-2019-nCoV Spike Neutralizing antibodies (Nabs) and Spike RBD protein binding validation

Figure. The binding of GeneMedi’s anti-2019-nCoV Spike Neutralizing antibodies (Nabs) to Recombinant 2019-nCoV(SARS-CoV-2) Spike RBD protein (GMP-V-2019nCoV-SRBD001) at 5.0ug/ml (100uL/well) was measured by ELISA.

A.
GMP-V-2019nCoV-SnAb001:Anti-2019-nCoV Spike (Spike RBD domain) human monoclonal neutralizing antibody (IgG1)
B.
GMP-V-2019nCoV-SnAb002:Anti-2019-nCoV Spike (Spike RBD domain) human monoclonal neutralizing antibody (IgM)
C.
GMP-V-2019nCoV-SnAb003:Anti-2019-nCoV Spike (Spike RBD domain) human monoclonal neutralizing antibody (IgA)
D.
GMP-V-2019nCoV-SnAb004:Anti-2019-nCoV Spike (Spike RBD domain) mouse monoclonal neutralizing antibody (IgG1)
E.
GMP-V-2019nCoV-SnAb005:Anti-2019-nCoV Spike (Spike RBD domain) Cynomolgus monoclonal neutralizing antibody (IgG1)
Figure. GeneMedi’s anti-2019-nCoV Spike Neutralizing antibodies (Nabs) block Recombinant 2019-nCoV(SARS-CoV-2) Spike RBD protein (GMP-V-2019nCoV-SRBD001) and hACE2 (GMP-H-ACE2002) binding.

A.
GMP-V-2019nCoV-SnAb001:Anti-2019-nCoV Spike (Spike RBD domain) human monoclonal neutralizing antibody (IgG1)
B.
GMP-V-2019nCoV-SnAb002:Anti-2019-nCoV Spike (Spike RBD domain) human monoclonal neutralizing antibody (IgM)
C.
GMP-V-2019nCoV-SnAb003:Anti-2019-nCoV Spike (Spike RBD domain) human monoclonal neutralizing antibody (IgA)
D.
GMP-V-2019nCoV-SnAb004:Anti-2019-nCoV Spike (Spike RBD domain) mouse monoclonal neutralizing antibody (IgG1)
E.
GMP-V-2019nCoV-SnAb005:Anti-2019-nCoV Spike (Spike RBD domain) Cynomolgus monoclonal neutralizing antibody (IgG1)

GeneMedi’s efficacy evaluation solutions will be useful for your anti-COVID-19 candidates funtional assay and evaluation,which is including:
1) Types of Vaccines (by testing immunized serum from human, mouse, NHP etc.)
2) Neutralizing antibodies
3) Peptides blockers (peptide inhibitors)
4) Compounds targeting Spike induced cell-fusion.

New variant of SARS-COV-2 (2019nCOV) B.1.1.7 lineage spreaded in UK

The world is in midst of the COVID-19 pandemic. Recently a novel SARS-COV-2 (2019nCOV) lineage, the B.1.1.7 lineage, with serials of site mutation, shows stronger infection ability in the UK. The SARS-COV-2 B.1.1.7 lineage carries a larger than a usual number of coronavirus genetic changes.

Extended Reading: Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations

Relative products collection:

GeneMedi products for New variant of SARS-COV-2 (2019nCOV) UK B.1.1.7 lineage

New variant of SARS-COV-2 (2019nCOV) 501Y.V2 lineage(B.1.351) spreaded in South African SARS-CoV-2

The South African variant is characterized by eight lineage-defining mutations in the spike protein including three key residues in the receptor binding domain (K417N, E484K and N501Y) and is referred to as lineage 501Y.V2.

Extended Reading: Alert Notification: New SARS-CoV-2 variant with multiple spike protein mutations

Relative products collection:
GeneMedi products for New variant of SARS-COV-2 (2019nCOV) South Africa 501Y.V2 lineage(B.1.351)

About COVID-19 Pandemic and SARS-CoV-2 Vaccine

Coronavirus Disease 2019 (COVID-19) is a novel viral pneumonia caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). First discovered in Wuhan, a city in Hubei province of China, COVID-19 has already broken out throughout the world and posed a great threat to the public health, especially in Europe and North America now. Additionally, person-to-person transmission of COVID-19 disease is reported to be extremely rapid [158-160]. To date, more than one million cases were infected with COVID-19 and over 55,000 deaths occurred. Therefore, it is really urgent and noteworthy to develop the vaccines specific to COVID-19/SARS-CoV-2.

Belonging to the Betacoronavirus genus family, SARS-CoV-2 is 60~200nm in diameter and encapsidates a large positive-sense, single-stranded RNA virus (26-32kb) with many spikes on the virus capsid (Fig. 17A). The RNA genome of SARS-CoV-2 encodes several accessory proteins and structural proteins, such as nucleocapsid (N) protein, envelope (E) protein, membrane (M) protein, and spike (S) protein (Fig. 10B). Although the detailed mechanism of SARS-CoV-2 infection has not been clearly illuminated, several studies demonstrated that SARS-CoV-2 enters human cells via utilizing spike (S) protein to bind to the angiotensin converting enzyme (ACE2) on the surface of target cell [161, 162].

Figure S1. SARS-CoV-2 capsid structure and genome map. (A) Three-dimensional structure diagram of SARS-CoV-2. (B) Genome organization of SARS-CoV-2 [158]. ORF: open reading frame. E: envelope. M: membrane. N: nucleocapsid. HR1: heptad repeat 1. HR2: heptad repeat 2. SP: signal peptide. NTD: N-terminal domain. RBD: receptor binding domain. S: spike. S1: subunit 1. S2: subunit 2. TM: transmembrane domain.

Since the genome sequences of SARS-CoV were discovered and reported (https://www.gisaid.org/CoV2020/), a large number of pharmaceutical enterprises and research organizations are sparing all efforts to the vaccine development. Different companies utilize different targets and antigen epitopes. Some of the advances are listed in the following Table 10 (from WHO), and most of them focus on viral vector-based vaccines (replicating or non-replicating viral vector-based vaccines), recombinant protein (Spike), and nucleic acid-based vaccines. To date, two COVID-19 vaccines have entered Phase I clinical testing to assess the safety and potency of vaccines. One is mRNA-1273, was developed by Moderna Therapeutics, encoding a prefusion-stabilized form of Spike (S) protein [163] (https://www.nature.com/articles/d41587-020-00005-z). Another vaccine is recombinant protein of SARS-CoV-2 antigen, developed by Chinese Academy of Military Sciences, Institute of Military Medicine. It was predicted that these vaccines can be applied in clinics in a large scale as early as 2021 if they can successfully pass the clinical testing. Although there is a long way for theses vaccines to be applied for prevention and therapy of COVID-19, they indeed bring great hope and light to people all over the world.

References

1. 2 Korber, B. et al. Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2. bioRxiv Preprint., doi:10.1101/2020.04.29.069054 (2020).

2. Investigation of novel SARS-COV-2 variant. Public health England.

3. European Centre for Disease Prevention and Control. Rapid increase of a SARS-CoV-2 variant with multiple spike protein mutations observed in the United Kingdom – 20 December 2020.ECDC: Stockholm; 2020.

4. Li, G. & De Clercq, E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nature Reviews Drug Discovery, doi:10.1038/d41573-020-00016-0 (2020).

5. Haque, A. & Pant, A. B. Efforts at COVID-19 Vaccine Development: Challenges and Successes. Vaccines 8, doi:10.3390/vaccines8040739 (2020).

6. Dong, Y. et al. A systematic review of SARS-CoV-2 vaccine candidates. Signal Transduction and Targeted Therapy 5, doi:10.1038/s41392-020-00352-y (2020).

7. Andrew Rambaut1, N. L., Oliver Pybus, Wendy Barclay, Jeff Barrett5, Alesandro Carabelli6, Tom Connor, Tom Peacock, David L Robertson8, Erik Volz,. Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations. https://virological.org/ (2020).

8. Rapid increase of a SARS-CoV-2 variant with multiple spike protein mutations observed in the United Kingdom. European Centre for Disease Prevention and Control: Publications & data.

9. Zhang, L. et al. SARS-CoV-2 RNA reverse-transcribed and integrated into the human genome. bioRxiv Preprint. , doi:10.1101/2020.12.12.422516 (2020).