BIODEGRADABLE HIGH-EFFICIENCY DENGUE VACCINE, METHOD FOR MAKING THE SAME, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

• US 20140193446A1
• Filed: 06/24/2013
• Published: 07/10/2014
• Est. Priority Date: 01/09/2013
• Status: Abandoned Application

• Current Assignee: National Cheng KUNG University (Government of The Republic of China)
• Original Assignee: National Cheng KUNG University (Government of The Republic of China)
• Inventors: LIN, YEE-SHIN, CHEN, YU-HUNG
• Application Number:
  US13/924,793
• Publication Number:
  US 20140193446A1
• Time in Patent Office: Days
• US Class Current: 424/186.1
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 2039/6031 Proteins
• CPC Class Codes: A61K 2039/6093 Synthetic polymers, e.g. polyethyleneglycol [PEG], Polymers or copolymers of (D) glutamate and (D) lysine
• CPC Class Codes: A61K 2039/64 characterised by the architecture of the carrier-antigen complex, e.g. repetition of carrier-antigen units
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 47/6921 the form being a particulate, a powder, an adsorbate, a bead or a sphere
• CPC Class Codes: A61K 47/6933 the polymer being obtained by reactions only involving carbon to carbon, e.g. poly(meth)acrylate, polystyrene, polyvinylpyrrolidone or polyvinylalcohol
• CPC Class Codes: A61K 47/6939 the polymer being a polysaccharide, e.g. starch, chitosan, chitin, cellulose or pectin
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: C12N 2770/24134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention is related to a biodegradable high-efficiency dengue vaccine, a method for making the same, and a pharmaceutical composition comprising the same. The biodegradable high-efficiency dengue vaccine comprises a biodegradable nanocomplex with electric properties holding a dengue viral protein inside. An organism has antibody responses after vaccination with the biodegradable nanocomplex twice. Accordingly, in comparison with the Alum adjuvant and Ribi adjuvant used in the traditional dengue vaccine of the prior art, the vaccination times in the present invention is decreased to further reduce the vaccination cost, so the biodegradable high-efficiency dengue vaccine is good for being a commercial vaccine.

Claims

1. A biodegradable high-efficiency dengue vaccine, comprising:

a biodegradable nanocomplex with an electric property holding a dengue viral protein inside, wherein an organism has an antibody response after vaccination with the biodegradable nanocomplex twice.

2. The biodegradable high-efficiency dengue vaccine as claimed in claim 1, wherein the dose of the biodegradable nanocomplex is no more than 25 μ

g for a first vaccination.

3. The biodegradable high-efficiency dengue vaccine as claimed in claim 1, wherein the organism has an antibody titer of 32000 at least after a second vaccination with the biodegradable nanocomplex.

4. The biodegradable high-efficiency dengue vaccine as claimed in claim 3, wherein the organism has the antibody titer of 1:

256000 after the second vaccination with the biodegradable nanocomplex.

5. The biodegradable high-efficiency dengue vaccine as claimed in claim 1, wherein the dengue viral protein comprising:

a nonstructural chimeric protein DJ NS1, comprising;

a N-terminal amino acid 1-270 of a dengue virus nonstructural protein (DV NS1); and

a C-terminal amino acid 271-352 of a Japanese encephalitis virus nonstructural protein (JEV NS1).

6. The biodegradable high-efficiency dengue vaccine as claimed in claim 5, wherein the sequence similarity between the nonstructural chimeric protein DJ NS1 and the SEQ. ID. NO.1 is more than 90%.

7. The biodegradable high-efficiency dengue vaccine as claimed in claim 1, wherein the biodegradable nanocomplex is made from a chitosan with positive charge and a heparin or polyglutamic acid with negative charge.

13. A pharmaceutical composition comprising:

a biodegradable high-efficiency dengue vaccine as claimed in claim 1 or an addition salt thereof with a pharmaceutically acceptable base; and

at least one pharmaceutically acceptable excipient.

14. The pharmaceutical composition as claimed in claim 13. which is used for producing a vaccine or a drug for treating or preventing hemorrhagic dengue fever or dengue shock syndrome.

8. A method for making a biodegradable high-efficiency dengue vaccine, comprising the steps of:

preparing a first solution comprising a first biodegradable macromolecule with a first electric property;

dissolving a dengue viral protein with the same electric property as the first biodegradable macromolecule into the first solution to be a mixture solution with the first electric property;

preparing a second solution comprising a second biodegradable macromolecule with a second electric property, wherein the first electric property is opposite to the second electric property; and

adding the mixture solution into the second solution for forming a biodegradable nanocomplex by attraction force between the different electric properties, wherein the dengue viral protein is held in the biodegradable nanocomplex.

9. The making method as claimed in claim 8, wherein the first macromolecule is heparin or polyglutamic acid, and the first electric property is a negative charge.

10. The making method as claimed in claim 8, wherein the second macromolecule is chitosan or collagen, and the second electric property is a positive charge.

11. The making method as claimed in claim 8, wherein the dengue viral protein comprising:

a nonstructural chimeric protein DJ NS1, comprising;

a N-terminal amino acid 1-270 of a dengue virus nonstructural protein (DV NS

     1); and

a C-terminal amino acid 271-352 of a Japanese encephalitis virus nonstructural protein (JEV NS1).

12. The making method as claimed in claim 11, wherein the sequence similarity between the nonstructural chimeric protein DJ NS1 and the SEQ. ID. NO.1 is more than 90%.