Recombinant RSV antigens
This disclosure provides recombinant respiratory syncytial virus (RSV) antigens and methods for making and using them, including immunogenic compositions (e.g., vaccines) for the treatment and/or prevention of RSV infection.
1. A recombinant respiratory syncytial virus (RSV) antigen comprising an F2 domain and an F1 domain of an RSV F protein polypeptide with no intervening furin cleavage site wherein the polypeptide further comprises a heterologous trimerization domain positioned C-terminal to the F 1 domain.
2. The recombinant RSV antigen of claim 1 , wherein the F 2 domain comprises at least a portion of an RSV F protein polypeptide corresponding to amino acids 26-105 of the reference F protein precursor polypeptide (F 0 ) of SEQ ID NO:2.
3. The recombinant RSV antigen of claim 1 , wherein the F 1 domain comprises at least a portion of an RSV F protein polypeptide corresponding to amino acids 137-516 of the reference F protein precursor polypeptide (F 0 ) of SEQ ID NO:2.
4. The recombinant RSV antigen of claim 1 , wherein the F 2 domain comprises an RSV F protein polypeptide corresponding to amino acids 26-105 and/or wherein the F 1 domain comprises an RSV F protein polypeptide corresponding to amino acids 137-516 of the reference F protein precursor polypeptide (F 0 ) of SEQ ID NO:2.
5. The recombinant RSV antigen of claim 1 , wherein the RSV antigen is selected from the group of:
a) a polypeptide comprising SEQ ID NO:6;
b) a polypeptide with at least 80% sequence identity to SEQ ID NO:6, which polypeptide comprises an amino acid sequence corresponding to the RSV F protein polypeptide of a naturally occurring RSV strain;
c) a polypeptide with at least 95% sequence identity to SEQ ID NO:6, which polypeptide comprises an amino acid sequence that does not correspond to a naturally occurring RSV strain,
wherein the RSV antigen polypeptide maintains the characteristic of comprising no intervening furin cleavage site between the F2 domain and the F1 domain and comprising a heterologous trimerization domain.
6. The recombinant RSV antigen of claim 1 , further comprising a signal peptide.
7. The recombinant RSV antigen of claim 1 , wherein the heterologous trimerization domain comprises a coiled-coil domain.
8. The recombinant. RSV antigen of claim 7 , wherein the heterologous trimerization domain comprises an isoleucine zipper.
9. The recombinant RSV antigen of claim 1 , wherein the RSV antigen comprises at least one modification selected from:
(i) a deletion of at least one non-furin cleavage site;
(ii) a deletion of one or more amino acids of the pep27 domain; and
(iii) at least one substitution or addition of a hydrophilic amino acid in a hydrophobic domain of the F protein extracellular domain.
10. The recombinant RSV antigen of claim 1 , wherein the RSV antigen comprises a multimer of polypeptides.
11. The recombinant RSV antigen of claim 10 , wherein the RSV antigen comprises a trimer of polypeptides.
12. An immunogenic composition comprising the recombinant RSV antigen of claim 1 , and a pharmaceutically acceptable carrier or excipient.
13. The immunogenic composition of claim 12 , wherein the carrier or excipient comprises a buffer.
14. The immunogenic composition of claim 12 , further comprising an adjuvant
15. The immunogenic composition of claim 14 , wherein the adjuvant comprises at least one of: 3D-MPL, QS21, an oil-in-water emulsion, and an aluminum or calcium salt.
16. The immunogenic composition of claim 12 , wherein the immunogenic composition inhibits infection with Respiratory Syncytial Virus (RSV).
17. The immunogenic composition of claim 12 , further comprising at least one additional antigen of a pathogenic organism other than RSV.
18. A method for eliciting an immune response against Respiratory Syncytial Virus (RSV), the method comprising:
administering to a subject a composition comprising the immunogenic composition of claim 12 .
19. The method of claim 18 , wherein administering the composition comprising the RSV antigen elicits an immune response specific for RSV without enhancing viral disease following contact with RSV.
20. The immunogenic composition of claim 15 , wherein the adjuvant comprises 3D-MPL and Alum.