Modified RSV F proteins and methods of their use
The present invention is generally related to modified or mutated respiratory syncytial virus fusion (F) proteins and methods for making and using them, including immunogenic compositions such as vaccines for the treatment and/or prevention of RSV infection.
1. A respiratory syncytial virus (RSV) fusion (F) protein comprising:
(i) a deletion of 10 acids corresponding to amino acids 137-146 of the wild-type RSV F protein (SEQ ID NO: 2); and
(ii) an inactivated primary furin cleavage site, corresponding to amino acids 131-136 of the wild-type RSV F protein (SEQ ID NO: 2), wherein the primary furin cleavage site is inactivated by substituting the amino acids at positions corresponding to arginine 133, arginine 135, and arginine 136 of the wild-type RSV F protein (SEQ ID NO: 2) with glutamine, and
wherein the RSV F protein is encoded by a nucleic acid having the sequence of SEQ ID NO: 7.
2. The RSV F protein of claim 1 , wherein the RSV F protein exhibits an increase in expression in a host cell as compared to the wild-type RSV F protein (SEQ ID NO: 2) expressed in the host cell, and wherein the host cell is an Sf9 cell.
3. The RSV F protein of claim 1 , wherein the RSV F protein exhibits reduced cellular toxicity in a host cell as compared to the wild-type RSV F protein (SEQ ID NO: 2) expressed in the host cell, and wherein the host cell is an Sf9 cell.
4. The RSV F protein of claim 1 , wherein the RSV F protein exhibits enhanced immunogenic properties as compared to the wild-type RSV F protein (SEQ ID NO: 2) when administered to a subject.
5. A pharmaceutically acceptable vaccine composition comprising a RSV F protein of claim 1 , and a pharmaceutically acceptable carrier, wherein the RSV F protein is capable of eliciting an immune response in a host.
6. The vaccine composition of claim 5 further comprising an adjuvant.
7. The vaccine composition of claim 6 wherein the adjuvant is an alum.
8. A purified micelle comprising a RSV F protein according to claim 1 .
9. A pharmaceutically acceptable vaccine composition comprising a purified micelle according to claim 8 , and a pharmaceutically acceptable carrier, wherein the micelle is capable of eliciting an immune response in a host.
10. The vaccine composition of claim 9 further comprising an adjuvant.
11. The vaccine composition of claim 10 wherein the adjuvant is an alum.
12. The RSV F protein of claim 1 wherein the RSV F protein lacks an N-terminal signal peptide.
13. A pharmaceutically acceptable vaccine composition comprising a RSV F protein of claim 12 , and a pharmaceutically acceptable carrier.
14. The vaccine composition of claim 13 further comprising an adjuvant.
15. The vaccine composition of claim 5 wherein the adjuvant is an alum.