Mature virus-like particles of flaviviruses
AssigneesChiang Mai University, National Science and Technology Development Agency (NSTDA)
InventorsNopporn Sittisombut, Malinee Sae-Lim, Nicha Charoensri, Poonsook Keelapang
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Abstract
Modified and expressed virus-like particles are described that are 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 set 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.
Claims11
A virus-like particle capable of eliciting an immune response in a mammal comprising a polypeptide, wherein the polypeptide comprises modified forms of both membrane (M) and envelope (E) structural proteins of a flavivirus, wherein the flavivirus comprises a dengue virus and a Japanese encephalitis virus, wherein the E structural protein of the dengue virus is fused to a peptide of the Japanese encephalitis virus;
- and
- wherein the modified forms of both the M and E structural proteins comprise one or more amino acid substitutions, wherein the one or more amino acid substitutions comprise a His to Ala substitution at one or more positions corresponding to H7, H336, H357, and H392 of SEQ ID NO:
- 9-11, or a His to Ala substitution at one or more positions corresponding to H7, H334, H355, and H390 of SEQ ID NO:
- 12.
An isolated polynucleotide encoding a virus-like particle or polypeptide capable of eliciting immune response in a subject upon administrating the virus-like particle or polypeptide to the subject at a pharmaceutically effective dosage, the virus-like particle or polypeptide comprising a modified form of both membrane (M) and envelope (E) structural proteins of a dengue virus fused to a peptide from a Japanese encephalitis virus, wherein a nucleotide sequence of the modified form corresponds to a sequence set forth in SEQ ID NO:
- 5, SEQ ID NO:
- 6, SEQ ID NO:
- 7 or SEQ ID NO:
- 8, or an amino acid sequence of the modified form corresponds to a sequence set forth in SEQ ID NO:
- 9-12, wherein SEQ ID NO:
- 9-11 comprise one or more His to Ala substitutions at positions H7, H336, H357, and H392 or SEQ ID NO:
- 12 comprises one or more His to Ala substitutions at positions H7, H334, H355 and H390.
A vaccine composition comprising:
- pharmaceutically acceptable adjuvant;
- and polypeptides or virus-like particles, which are immunologically active upon administrating to a subject, having an amino acids sequence corresponding to SEQ ID NO:
- 9, SEQ ID NO:
- 10, SEQ ID NO:
- 11, or SEQ ID NO:
- 12, wherein the amino acids sequence comprises a modified form of dengue virus sequence comprising a His to Ala substitution at one or more of positions H7, H336, H357, and H392 in SEQ ID NO:
- 9-11, or a His to Ala substitution at one or more of positions H7, H334, H355, and H390 in SEQ ID NO:
- 12.
A vaccine composition comprising a pharmaceutically acceptable adjuvant and either a nucleic acid or polypeptide, wherein the nucleic acid comprises a nucleotide sequence as set forth in SEQ ID NO:
- 5, SEQ ID NO:
- 6, SEQ ID NO:
- 7 or SEQ ID NO:
- 8, respectively, or wherein the polypeptide comprises a sequence as set forth in SEQ ID NO:
- 1, SEQ ID NO:
- 2, SEQ ID NO:
- 3 and SEQ ID NO:
- 4.
Dependencies are inferred from the claim text.