Abstract: The present disclosure associates to a modified and expressed virus-like particles. Particularly, the virus-like particle is capable of eliciting immune response in a mammal upon administrating a pharmaceutically efficient dosage to the mammal. The virus-like particle comprises a modified form of M and E structural proteins of flavivirus. Further, the virus-like particle comprises an amino acids sequence substantially corresponding to a sequence setting forth in SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3 or SEQ ID NO. 4, wherein conserved and internally located His at multiple positions of the M and E proteins are substituted with uncharged residues, and other secretion-enhancing substitutions are introduced.

Abstract: The invention includes a genetic construct and a mutant dengue virus, designated as strain MBU 01-2002, which is a mutant dengue virus generated by genetic modification of the 13-amino acid sequence just proximal to the pr-M junction within the prM coding region of the genome. The modification involves increasing the number of positively charged amino acids and abolishing the negatively charged amino acids in this pr-M junction sequence. The mutant dengue virus strain MBU 01-2002 possesses less prM protein on the viral envelope than the prototype dengue virus, is capable of inducing infected C6/36 cells to fuse at neutral pH, is as efficient as the prototype virus in the intracellular multiplication, but is defective in its release from infected cells.

Abstract: The invention includes a genetic construct and a mutant dengue virus, designated as strain MBU 01-2002, which is a mutant dengue virus generated by genetic modification of the 13-amino acid sequence just proximal to the pr-M junction within the prM coding region of the genome. The modification involves increasing the number of positively charged amino acid and abolishing the negatively charged amino acid in this pr-M junction sequence. The mutant dengue virus strain MBU 01-2002 possesses less prM protein on the viral envelope than the prototype dengue virus, is capable of inducing infected C6/36 cells to fuse at neutral pH, is as efficient as the prototype virus in the intracellular multiplication, but is defective in its release from infected cells.