RSV F protein mutants
The present disclosure relates to RSV F protein mutants, nucleic acids or vectors encoding a RSV F protein mutant, compositions comprising a RSV F protein mutant or nucleic acid, and uses of the RSV F protein mutants, nucleic acids or vectors, and compositions.
1. A method of preventing Respiratory Syncytial Virus (RSV) infection in a human infant comprising administering to a pregnant woman an effective amount of a pharmaceutical composition comprising (1) a mutant of a wild-type RSV F protein and (2) a pharmaceutically acceptable carrier, wherein the mutant comprises (a) a F1 polypeptide and a F2 polypeptide and (b) at least one introduced amino acid mutation relative to the amino acid sequence of the wild-type RSV F protein, wherein the introduced amino acid mutation is a pair of cysteine mutations selected from the group consisting of: (i) 55C and 188C; (ii) 103C and 148C; and (iii) 142C and 371C, and wherein amino acid positions are numbered according to SEQ ID NO:1.
2. The method of claim 1 , wherein the pharmaceutical composition comprises: (1) a mutant of the F protein of a subtype-A wild-type RSV; (2) a mutant of the F protein of a subtype-B wild-type RSV; and (3) a pharmaceutically acceptable carrier, wherein each of the mutants comprises a F2 polypeptide and F1 polypeptide, wherein the F2 polypeptide and F1 polypeptide of the mutant of the F protein of the subtype-A wild-type RSV comprise the amino acid sequence of SEQ ID NO:45 and the amino acid sequence of SEQ ID NO:46, respectively, and wherein the F2 polypeptide and F1 polypeptide of the mutant of the F protein of the subtype-B wild-type RSV comprise the amino acid sequence of SEQ ID NO: 49 and the amino acid sequence of SEQ ID NO:50, respectively.
3. A method of eliciting an immune response against Respiratory Syncytial Virus (RSV) in a human infant comprising administering to a pregnant woman an effective amount of a pharmaceutical composition comprising a mutant of a wild-type RSV F protein and a pharmaceutically acceptable carrier, wherein the mutant comprises (a) a F1 polypeptide and a F2 polypeptide and (b) at least one introduced amino acid mutation relative to the amino acid sequence of the wild-type RSV F protein, wherein the introduced amino acid mutation is a pair of cysteine mutations selected from the group consisting of: (i) 55C and 188C; (ii) 103C and 148C; and (iii) 142C and 371C, and wherein amino acid positions are numbered according to SEQ ID NO:1.
4. The method of claim 3 , wherein the pharmaceutical composition comprises: (1) a mutant of the F protein of a subtype-A wild-type RSV; (2) a mutant of the F protein of a subtype-B wild-type RSV; and (3) a pharmaceutically acceptable carrier, wherein each of the mutants comprises a F2 polypeptide and F1 polypeptide, wherein the F2 polypeptide and F1 polypeptide of the mutant of the F protein of the subtype-A wild-type RSV comprise the amino acid sequence of SEQ ID NO:45 and the amino acid sequence of SEQ ID NO:46, respectively, and wherein the F2 polypeptide and F1 polypeptide of the mutant of the F protein of the subtype-B wild-type RSV comprise the amino acid sequence of SEQ ID NO:49 and the amino acid sequence of SEQ ID NO:50, respectively.
5. The method according to claim 4 , wherein the C-terminus of the F1 polypeptide of the mutant is linked to a phage T4 fibritin foldon domain.
6. The method according to claim 5 , wherein the pharmaceutical composition further comprises an adjuvant.
7. The method according to claim 6 , wherein the adjuvant is aluminum hydroxide.
8. The method according to claim 4 , wherein the human infant is a newborn.
9. The method according to claim 4 , wherein the human infant is an infant in utero.
10. The method according to claim 5 , wherein the human infant is a newborn.
11. The method according to claim 5 , wherein the human infant is an infant in utero.
12. The method according to claim 2 , wherein the C-terminus of the F1 polypeptide of the mutant is linked to a phage T4 fibritin foldon domain.
13. The method according to claim 12 , wherein the pharmaceutical composition further comprises an adjuvant.
14. The method according to claim 13 , wherein the adjuvant is aluminum hydroxide.
15. The method according to claim 2 , wherein the human infant is a newborn.
16. The method according to claim 2 , wherein the human infant is an infant in utero.
17. The method according to claim 12 , wherein the human infant is a newborn.
18. The method according to claim 12 , wherein the human infant is an infant in utero.