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Information of Monkeypox virus (MPV)

Prevalence and Perniciousness of MPV

Monkeypox is a rare disease that is caused by infection with monkeypox virus. Monkeypox virus belongs to the Orthopoxvirus genus in the family Poxviridae. The Orthopoxvirus genus also includes variola virus (which causes smallpox), vaccinia virus (used in the smallpox vaccine), and cowpox virus. Monkeypox was first discovered in 1958 when two outbreaks of a pox-like disease occurred in colonies of monkeys kept for research, hence the name ‘monkeypox.’ The first human case of monkeypox was recorded in 1970 in the Democratic Republic of the Congo (DRC). Since then, monkeypox has been reported in people in several other central and western African countries: Cameroon, Central African Republic, Cote d’Ivoire, Democratic Republic of the Congo, Gabon, Liberia, Nigeria, Republic of the Congo, and Sierra Leone. Monkeypox cases in people have occurred outside of Africa linked to international travel or imported animals, including cases in the United States, as well as Israel, Singapore, and the United Kingdom.

Genome of MPV and other Pox viruses

Poxviruses have base-paired DNA genomes that range in size from 130 to 300 kbp. They encode all enzymes needed for RNA and DNA synthesis and replicate in the cell cytoplasm. Poxviruses are also masters of evading innate and adaptive immune responses, using a variety of proteins encoded by their large genomes. Virions are enveloped, their surfaces covered with proteinaceous ridges or tubules. Virion morphology is often referred to as complex and they contain 70–80 structural proteins. Virions have multiple envelope proteins, with obvious transmembrane domains, but notably, none are glycosylated. Based on genomic comparisons of several monkeypox virus strains, five genes—D10L (host range protein), D14L (complement inhibitor), B10R (apoptotic regulator), B14R (interleukin [IL]-1β binding protein), and B19R (serine protease inhibitor-like protein)—have been speculated to be most likely responsible for the increased virulence of monkeypox virus.

Diagnostics of MPV infection

Monkeypox can be tentatively diagnosed if the characteristic skin lesions are present, or if other symptoms consistent with the disease are seen during an outbreak. The diagnosis can be confirmed by histopathology and virus isolation. Polymerase chain reaction (PCR) is the preferred laboratory test given its accuracy and sensitivity. For this, optimal diagnostic samples for monkeypox are from skin lesions or fluid from vesicles and pustules, and dry crusts. An antibody based serological assay is ideal for diagnostics and surveillance, but due to antigen conservation within OPXV genomes, most serum is cross-reactive and cannot differentiate between individual species of OPXVs. To identify potential epitopes, candidate genes such as D2L, B18R, N2R, N3R and B21R, were identified in monkeypox that are not present in the vaccinia genome were used as overlapping peptides for screening linear antibody epitopes. Among them, B21R gene product (1,879 amino acids) was highly immunogenic, epitopes with 100% sensitivity with recent MPV has been developed and used to detect the MPV infection.

MPV therapeutics and vaccine

At present, there are no specific treatments available for monkeypox infection, but monkeypox outbreaks can be controlled. Smallpox vaccine, cidofovir, ST-246, and vaccinia immune globulin (VIG) can be used to control a monkeypox outbreak. Though monkeypox virus is closely related to the virus that causes smallpox, smallpox vaccine can also protect people from getting monkeypox. Past data from Africa suggests that smallpox vaccine is at least 85% effective in preventing monkeypox. 

Monkeypox virus (MPV) antibodies for therapeutics Discovery (MPV Neutralizing antibody, Benchmark) and Diagnosis

Description of A25/A28/A33/B5/L1/H3: structure, location and function in MPV

The A33, L1, B5, and A25 genes encode the four proteins viz. A33, L1, B5, and A25, respectively. All of these immunogens are highly homologous (> 93%) between variola, monkeypox, and vaccinia. A33 is a type II integral membrane protein present as a dimer on the EV. Some evidence suggests A33 has a role in facilitating antibody-resistant cell-to-cell spread of orthopoxviruses. The A28 gene of vaccinia virus is conserved in all poxviruses and encodes a protein that is anchored to the surface of infectious intracellular mature virions (IMV) and consequently lies beneath the additional envelope of extracellular virions and required for the virus propagation. The product of the H3L gene, p35, is another envelope protein that is an immunodominant antigen found on orthopoxvirus. Strong immune responses to p35 protein have been detected in mice, sheep, rabbits, and humans. It has also been shown that the monoclonal antibodies against A28, A33, B5, L1 and H3 are cross protective cross-protective for variola, monkeypox, and vaccinia.

GeneMedi has quickly screened these neutralizing antibodies, which are valid for Monkeypox virus (MPV). They could be used as Benchmark Antibody, assist in neutralizing antibody discovery and development. They could also be used for Diagnosis. It should be noted that these antibodies have cross reactivity with vaccinia virus (VACV) and other Pox viruses.

Furthermore, the epitope of A29 has been designed specific for monkeypox virus. GeneMedi has quickly developed the antibody pair of MPV A29 to help accelerate the MPV diagnosis.

Cat No.

Target

Product Name (Neutralizing antibody Name)

Source (Expression Host)

Order

GMP-MPV-Tg01-nAb001,
GMP-MPV-Tg01-nAb002,
GMP-MPV-Tg01-nAb003,
GMP-MPV-Tg01-nAb004
A33Anti-MPV (A33) human monoclonal neutralizing antibody (IgG1)Mammalian (human cell)Picture loading failed.
GMP-MPV-Tg02-nAb001,
GMP-MPV-Tg02-nAb002,
GMP-MPV-Tg02-nAb003,
GMP-MPV-Tg02-nAb004,
GMP-MPV-Tg02-nAb005,
GMP-MPV-Tg02-nAb006
B5Anti-MPV (B5) human monoclonal neutralizing antibody (IgG1)Mammalian (human cell)Picture loading failed.
GMP-MPV-Tg03-nAb001,
GMP-MPV-Tg03-nAb002,
GMP-MPV-Tg03-nAb003,
GMP-MPV-Tg03-nAb004,
GMP-MPV-Tg03-nAb005
L1Anti-MPV (L1) human monoclonal neutralizing antibody (IgG1)Mammalian (human cell)Picture loading failed.
GMP-MPV-Tg04-nAb001A25Anti-MPV (A25) human monoclonal neutralizing antibody (IgG1)Mammalian (human cell)Picture loading failed.
GMP-MPV-Tg05-nAb001A28Anti-MPV (A28) human monoclonal neutralizing antibody (IgG1)Mammalian (human cell)Picture loading failed.
GMP-MPV-Tg06-nAb001H3Anti-MPV (H3) human monoclonal neutralizing antibody (IgG1)Mammalian (human cell)Picture loading failed.
GMP-MPV-Tg07-Ab001,
GMP-MPV-Tg07-Ab002
A29Anti-MPV (A29) human monoclonal antibody (IgG1)Mammalian (human cell)Picture loading failed.

Monkeypox virus (MPV) peptides antigens for specific MPV Diagnosis

Description of A29/B21R: structure, location and function in MPV

Vaccinia virus envelope protein A27 has multiple functions and is conserved in the Orthopoxvirus genus of the poxvirus family. A27 protein binds to cell surface heparan sulfate, provides an anchor for A26 protein packaging into mature virions, and is essential for egress of mature virus (MV) from infected cells. A27 is homolog of monkeypox virus A29. The epitope of A29 has been designed specific for monkeypox virus. In addition, the large immunogenic surface glycoprotein B21R of monkeypox viruses are specifically detected only in the monkeypox virus are useful for distinguishing monkeypox from previous vaccinia vaccination and other Orthopoxvirus. These epitopes have been used for detection of monkey pox virus.

GeneMedi has quickly designed the peptides antigens of MPV to help accelerate the MPV diagnostic, vaccine and therapeutic antibody discovery and development.

Cat No.

Target

Product Name (Antigen Name)

Source

Order

GMP-MPV-Tg07-Ag001

A29

MPV A29 protein antigen

E.coli - based prokaryotic cell expression system

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GMP-MPV-Tg08-Ag001

B21R

MPV B21R peptide antigen

synthesized

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Pseudotype virus (pseudovirus, PSV) of Monkeypox virus (MPV)

Description of F3L/B6R: structure, location and function in MPV

The MPXV F3 protein is a homologue of the VACV E3 protein, with nucleotide and protein sequence identities of 92% and 88%, respectively. The genomic sequence of MPXV suggests that the F3 protein contains a complete, functional, C-terminal dsRNA-binding domain, while the first 37 amino acids of the N terminus of the Z-NA binding domain are deleted. The VACV E3L gene has been shown to play a critical role in inhibiting the cellular interferon (IFN) antiviral immune response. The E3 protein is able to bind double-stranded RNA (dsRNA) and sequester it away from known pattern recognition receptors (PRRs; e.g., protein kinase R [PKR], RIG-I, MDA-5, and OAS), thereby preventing their activation. Even though the MXPV genome encodes an altered E3 homologue, MPXV has an IFNr and host range phenotype similar to that of wt VACV and it is able to inhibit the cellular antiviral immune response. B6R is the envelope protein of the monkeypox virus. Due to the advantage of single nucleotide polymorphisms within a small sequence of the monkeypox virus B6R, B6R primers and probe are designed completely homologous with the monkeypox (CB) DNA sequence. The F3L and B6R assay did not cross-react with any other orthopoxviral DNA (variola, cowpox, camelpox, and vaccinia). Overall, the F3L and B6R assay demonstrates a sensitive, specific, and rapid method for identifying MPXV. Using discrete viral gene targets, these assays provide a reliable and sensitive method for quickly confirming monkeypox infections.

To face with the epidemic of monkeypox virus (MPV), many in vitro diagnostic companies launched monkeypox virus nucleic acid test (NAT) kits. Taking responsibility to help accelerate the Monkeypox virus (MPV) Diagnosis, GeneMedi had developed the pseudotype virus (pseudovirus, PSV) of Monkeypox virus (MPV), which will be used as quality control/positive control products for Monkeypox nucleic acid test (NAT) detection.

Cat No.

Target

Pseudotyped virus of Monkeypox virus (MPV)

Vector

Order

GM-MPV-Tg09-PSV01

F3L

MPV F3L Pseudotyped virus (pseudovirus, PSV)

AAV

Picture loading failed.

GM-MPV-Tg10-PSV02

B6R

MPV B6R Pseudotyped virus (pseudovirus, PSV)

AAV

Picture loading failed.





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