Designing a Multi-Epitope Subunit Vaccine against VP1 Major Coat Protein of JC Polyomavirus

Abstract

The JC polyomavirus virus (JCPyV) affects more than 80% of the human population in their early life stage. It mainly affects immunocompromised individuals where virus replication in oligodendrocytes and astrocytes may lead to fatal progressive multifocal encephalopathy (PML). Virus protein 1 (VP1) is one of the major structural proteins of the viral capsid, responsible for keeping the virus alive in the gastrointestinal and urinary tracts. VP1 is often targeted for antiviral drug and vaccine development. Similarly, this study implied immune-informatics and molecular modeling methods to design a multi-epitope subunit vaccine targeting JCPyV. The VP1 protein epitopic sequences, which are highly conserved, were used to build the vaccine. This designed vaccine includes two adjuvants, five HTL epitopes, five CTL epitopes, and two BCL epitopes to stimulate cellular, humoral, and innate immune responses against the JCPyV. Furthermore, molecular dynamics simulation (100 ns) studies were used to examine the interaction and stability of the vaccine protein with TLR4. Trajectory analysis showed that the vaccine and TLR4 receptor form a stable complex. Overall, this study may contribute to the path of vaccine development against JCPyV.

Polyomavirus Wakes Up and Chooses Neurovirulence

“…Sensing is performed by PRRs, a diverse group of receptors that sense either extracellular or intracellular molecules associated with pathogens. On the extracellular front, TLRs, especially TLR4 and TLR9, are important in sensing neuropathic polyomaviruses like JCPyV and MuPyV [ 247 , 248 , 249 , 250 ]. One JCPyV vaccine study has looked into the interaction of TLR4 with JCPyV VP1 capsid protein as a mechanism of priming immunity [ 249 ].…”

“…On the extracellular front, TLRs, especially TLR4 and TLR9, are important in sensing neuropathic polyomaviruses like JCPyV and MuPyV [ 247 , 248 , 249 , 250 ]. One JCPyV vaccine study has looked into the interaction of TLR4 with JCPyV VP1 capsid protein as a mechanism of priming immunity [ 249 ]. Single nucleotide polymorphisms in TLR3 and 4 contribute to BKPyV viremia in transplant patients [ 251 , 252 ].…”