Recombinant Poliovirus type 1 VP1 Protein [His]

Poliomyelitis is a disease caused by infection with the polio virus. Clinical studies have shown that its main symptoms are fever, upper respiratory tract symptoms, and limb pain. Studies have shown that the virus mainly invades the gray matter and white matter of the anterior horn of the human spinal cord and causes permanent damage to the gray matter. This damage can cause flaccid paralysis of the limbs. Some patients develop flaccid neuropathy and are left with permanent paralysis. The disease is preventable and difficult to treat, and once it has caused limb paralysis, it can easily lead to lifelong disability or even life-threatening conditions. Vaccination is the most cost-effective and effective way to prevent and control the spread of the disease. Poliovirus (PV), first discovered in 1909, is a member of the Picornaviridae family and belongs to the Enterovirus C group. It is a crippling virus. PV has a diameter of 25-30 nm. Each of the 60 capsids that make up its capsid or outer layer consists of the virion proteins VP1, VP2, VP3 and VP4, which are organized in an icosahedral pattern. Three serotypes of PV have been recognized: type 1, type 2 and type 3. The PV genome is a 7.4 kb RNA molecule with an open reading frame (ORF) and 5' and 3' untranslated regions (UTRs) of approximately 70 to 740 nt each. The ORF encodes a polyprotein of approximately 2200 residues, which is ultimately converted by viral proteolytic activity into 11 'mature' polypeptides, with some intermediate processing steps acting as discrete functional units. The final four polypeptides (VP1-VP4) correspond to the N-terminus of the polyprotein and are structural components of the viral capsid. The remaining polypeptides are directly or indirectly involved in viral genome replication, polypeptide proteolytic processing and various activities that ensure efficient viral progeny production.

Figure 1. Schematic representation of the capsid and genome of poliovirus. (Sources: Combelas N, et al. 2011)

The only known natural reservoir of PV is humans. The fecal-oral route is the mode of transmission of the disease. After local growth in the tonsils and cervical lymph nodes, PV subsequently spreads to the lymph nodes and small intestine. The virus multiplies in the pharynx and intestines for 1 to 3 weeks. The usual incubation period is 2 to 35 days. The virus is excreted in the feces after 3 to 5 days and can also be recovered from throat swabs of exposed patients. Local immune responses usually prevent the spread of the virus. Therefore, in about 95% of cases, the infection is either asymptomatic or marked by influenza-like symptoms. Gastroenteritis, respiratory tract infections, and influenza-like illnesses can all occur. Antibodies may cause a decline in viremia or may be transferred to the central nervous system (CNS) via the blood. The virus is most fully excreted in the feces 2 to 3 days before and 1 week after the onset of symptoms. In addition, according to published studies, the virus spreads along the afferent nerve pathways of the brain because it has a specific affinity for the cell receptor CD155, which promotes cell entry and attachment. The cytopathic nature of the virus leads to extensive destruction, such as severe damage to the anterior horn cells of the spinal cord, resulting in limb paralysis. Posterior horn cells, thalamic motor neurons, and hypothalamus are potential targets for viral transmission. Brainstem involvement in bulbar poliomyelitis can be fatal. Histological findings of damaged brain cells show vacuolation and infiltration, as well as accumulation of plasma cells, polymorphonuclear neutrophils, and microglia. Axonal degeneration is caused by macrophage phagocytosis of infected cells. Muscle atrophy is widespread, resulting in flaccid paralysis. In severe cases, respiratory paralysis usually leads to death. Post-polio syndrome (PPS) may develop 25 to 30 years after the first episode of paralysis. Progressive muscle atrophy is observed in PPS, most likely as a result of ongoing motor neuron degeneration. Another theory is that abnormal cytokine levels may be caused by the persistence of PV in the brain and spinal cord.

The PV VLP project was initiated by WHO and the University of Leeds in the UK. VLP particles are very similar to viruses, and they do not contain any viral genetic material (the RNA information of PV), so they are not infectious. Natural PV capsid protein does not form stable particles in the absence of RNA, so PV VLP requires transgenic capsid protein and the addition of stabilizing elements. Co-expression of poliovirus P1 capsid protein precursor and 3CD protease in different systems has been shown to effectively produce VLPs that can induce protective antibody responses. At present, the results of preclinical immunogenicity studies of PV VLPs with alum as an adjuvant have become similar or better immunogenicity than IPV in Wistar rats. Currently, due to cost considerations, WHO focuses on yeast and baculovirus as the expression platform for PV VLPs, which are the two expression systems most likely to produce vaccines at low cost.

Poliovirus VP1
VP1 Capsid Protein
Poliovirus Structural Protein VP1
Poliovirus Capsid Protein VP1
Type 1 Poliovirus VP1
VP1 Major Capsid Protein
Poliovirus Coat Protein VP1