Rabies glycoprotein virus-like particles (VLPS)
The present invention is generally related to virus-like particles (VLPs) comprising rabies virus (RV) glycoproteins (G proteins) and methods for making and using them, including immunogenic compositions such as vaccines for the treatment and/or prevention of rabies virus infection.
1. A pharmaceutical composition comprising rabies virus (RV) glycoproteins (G proteins) in a micellar particle with NP-9, wherein the G proteins form a trimer, wherein the G proteins are purified from an insect host cell, and a pharmaceutically acceptable carrier, diluent, or excipient.
2. The pharmaceutical composition of claim 1 , wherein the RV G protein comprises SEQ ID NO:2.
3. The pharmaceutical composition of claim 1 , wherein the RV G proteins are derived from an RV strain selected from human, canine, bat, raccoon, skunk, and fox.
4. The pharmaceutical composition of claim 1 , further comprising an adjuvant.
5. The pharmaceutical composition of claim 4 , wherein the adjuvant is an aluminum adjuvant.
6. The pharmaceutical composition of claim 1 , wherein the micellar particle increases the production of anti-G protein antibodies in a host.
7. The pharmaceutical composition of claim 6 , wherein the anti-G protein antibodies produced are neutralizing antibodies.
8. The pharmaceutical composition of claim 7 , wherein the anti-G protein antibodies produced are protective.
9. The pharmaceutical composition of claim 6 , wherein the micellar particle induces the production of anti-G protein antibodies in the host after administration of a single dose.
10. The pharmaceutical composition of claim 6 , wherein the micellar particle provides a seroprotective titer in 7 days.
11. A method of treating or preventing a rabies infection comprising administering to a host a micellar particle comprising rabies virus (RV) glycoproteins (G proteins), wherein the G proteins form a trimer, and wherein the micellar particles are purified from an insect host cell and comprises the detergent NP-9.
12. The method of claim 11 , wherein the micellar particle increases the production of anti-G protein antibodies in the host.
13. The method of claim 12 , wherein the anti-G protein antibodies produced are neutralizing antibodies.
14. The method of claim 13 , wherein the anti-G protein antibodies produced are protective.
15. The method of claim 12 , wherein the micellar particle induces the production of anti-G protein antibodies in the host after administration of a single dose.
16. The method of claim 12 , wherein the micellar particle provides a seroprotective titer in 7 days.
17. A method of making a micellar particle comprising rabies virus (RV) glycoproteins (G proteins), wherein the G proteins form a trimer comprising:
(a) transforming an insect host cell to express an isolated nucleic acid encoding a RV G protein; and
(b) culturing said host cell under conditions conducive to the production of said micellar particle; and
(c) purifying the micellar particle in the presence of the detergent NP-9.
18. The pharmaceutical composition of claim 1 wherein the insect cell is an Sf9 cell.