Respiratory syncytial virus (RSV) vaccine

Abstract

The present invention relates to a respiratory syncytial virus (RSV) vaccine, wherein the nucleic acid comprises a polynucleotide encoding a mutant of the RSV F protein that, when compared to the wild-type RSV F protein, includes one or more of the following mutations: disulfide bond mutations, cavity-filling mutations, and electrostatic mutations.

Claims

1. A nucleic acid comprising a polynucleotide encoding a mutant of the RSV F protein containing F1 polypeptide and F2 polypeptide, wherein, compared to the wild-type RSV F protein, the mutant includes one or more of the following mutations: disulfide bond mutations, cavity-filling mutations, and electrostatic mutations.

2. The disulfide bond mutations are as follows: S46C and T311C, A47C and I309C, L48C and V308C, S55C and L188C, V56C and T189C, V56C and V300C, I57C and S190C, I57C and Y299C, T58C and K191C, I59C and L193C, I59C and L297C, E60C and D194C, P10 Includes one or more of the following: 1C and I152C, A102C and I148C, A102C and I152C, T103C and I146C, T103C and I148C, N104C and G145C, N104C and S146C, N105C and G145C, N105C and S146C, N105C and A147C, V144C and V406C, and S146C and N460C; Preferably, the nucleic acid according to claim 1, wherein the disulfide bond mutation comprises one or more of the following: A47C and I309C, I57C and Y299C, P101C and I152C, A102C and I148C, A102C and I152C, T103C and I146C, N104C and G145C, N104C and S146C, N105C and G145C, N105C and S146C, and N105C and A147C.

3. The cavity-filling mutations are as follows: (1) to (3): (1) Substitution of T at position 54 with F, W, V, C, A, H, I, Y, L, or M; preferably, substitution of T at position 54 with F, W, or V; (2) Substitution of S at position 190 by V, I, M, F, L, W, Y, H, R, E, A, Q, G, P, T, C, D, N or K; and (3) Substitution of V at position 296 by I, L, Y, H, F, or M The nucleic acid according to claim 1 or 2, comprising one or more of the following.

4. The electrostatic mutations mentioned above are as follows: (1) Substitution of D at position 486 by Q, S, H, N, T, P, C, L, I, F, or W; and (2) Substitution of V at position 487 by Q, T, N, I, K, P, R, S, Y, D, F, L, H, or C A nucleic acid according to any one of claims 1 to 3, comprising one or more of the following.

5. The nucleic acid according to any one of claims 1 to 4, wherein the mutation of the mutant comprises at least one of a disulfide bond mutation, a cavity filling mutation, and an electrostatic mutation; preferably, the mutation of the mutant comprises a cavity filling mutation and a disulfide bond mutation.

6. The mutations in the mutant are (1) to (20) below: (1) A102C, I152C, T54V, S190M and V296L; (2) A102C, I152C, T54F, S190M and V296L; (3) A102C, I152C, T54C, S190M and V296L; (4) A102C, I152C, T54A, S190M and V296L; (5) A102C, I152C, T54V, S190F and V296L; (6) A102C, I152C, T54F, S190F and V296L; (7) A102C, I152C, T54C, S190F and V296L; (8) A102C, I152C, T54A, S190F and V296L; (9) P101C, I152C, T54V, S190M and V296L; (10) P101C, I152C, T54F, S190M and V296L; (11) P101C, I152C, T54C, S190M and V296L; (12) P101C, I152C, T54A, S190M and V296L; (13) P101C, I152C, T54V, S190F and V296L; (14) P101C, I152C, T54F, S190F and V296L; (15) P101C, I152C, T54C, S190F and V296L; (16) P101C, I152C, T54A, S190F and V296L; (17) A102C, I152C, T54V, S190I and V296L; (18) A102C, I152C, T54F, S190I and V296L; (19) A102C, I152C, T54C, S190I and V296L; and (20) A102C, I152C, T54A, S190I and V296L, A nucleic acid according to any one of claims 1 to 5, selected from the above.

7. The aforementioned mutants are (1) to (40) below: (1) Mutants containing the amino acid sequence shown in SEQ ID NO: 61 or 62; (2) Mutants comprising mutants A102C, I152C, T54V, S190M and V296L, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 61 or 62; (3) Mutants having the amino acid sequence shown in SEQ ID NO: 63 or 64; (4) Mutants comprising mutations A102C, I152C, T54F, S190M and V296L, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 63 or 64; (5) Mutants having the amino acid sequence shown in SEQ ID NO: 65 or 66; (6) Mutants comprising mutants A102C, I152C, T54C, S190M and V296L, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 65 or 66; (7) Mutants having the amino acid sequence shown in SEQ ID NO: 67 or 68; (8) Mutants comprising mutants A102C, I152C, T54A, S190M and V296L, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 67 or 68; (9) Mutants having the amino acid sequence shown in SEQ ID NO: 69 or 70; (10) Mutants comprising mutants A102C, I152C, T54V, S190F and V296L, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 69 or 70; (11) Mutants having the amino acid sequence shown in SEQ ID NO: 71 or 72; (12) Mutants comprising mutations A102C, I152C, T54F, S190F and V296L, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 71 or 72; (13) Mutants having the amino acid sequence shown in SEQ ID NO: 73 or 74; (14) Mutants comprising mutations A102C, I152C, T54C, S190F and V296L, and having an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 73 or 74; (15) Mutants having the amino acid sequence shown in SEQ ID NO: 75 or 76; (16) Mutants comprising mutations A102C, I152C, T54A, S190F and V296L, and containing an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 75 or 76; (17) Mutants having the amino acid sequence shown in SEQ ID NO: 77 or 78; (18) Mutants comprising mutants P101C, I152C, T54V, S190M and V296L, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 77 or 78; (19) Mutants having the amino acid sequence shown in SEQ ID NO: 79 or 80; (20) Mutants comprising mutants P101C, I152C, T54F, S190M and V296L, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 79 or 80; (21) Mutants having the amino acid sequence shown in SEQ ID NO: 81 or 82; (22) Mutants comprising mutants P101C, I152C, T54C, S190M and V296L, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 81 or 82; (23) Mutants having the amino acid sequence shown in SEQ ID NO: 83 or 84; (24) Mutants comprising mutants P101C, I152C, T54A, S190M and V296L, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 83 or 84; (25) Mutants having the amino acid sequence shown in SEQ ID NO: 85 or 86; (26) Mutants comprising mutants P101C, I152C, T54V, S190F and V296L, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 85 or 86; (27) Mutants having the amino acid sequence shown in SEQ ID NO: 87 or 88; (28) Mutants comprising mutants P101C, I152C, T54F, S190F and V296L, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 87 or 88; (29) Mutants having the amino acid sequence shown in SEQ ID NO: 89 or 90; (30) Mutants comprising mutants P101C, I152C, T54C, S190F and V296L, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 89 or 90; (31) Mutants having the amino acid sequence shown in SEQ ID NO: 91 or 92; (32) Mutants comprising mutants P101C, I152C, T54A, S190F and V296L, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in SEQ ID NO: 91 or 92; (33) Mutants having the amino acid sequence shown in SEQ ID NO: 93 or 94; (34) Mutants comprising mutations A102C, I152C, T54V, S190I and V296L, and having an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 93 or 94; (35) Mutants having the amino acid sequence shown in SEQ ID NO: 95 or 96; (36) Mutants comprising mutations A102C, I152C, T54F, S190I and V296L, and having an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 95 or 96; (37) Mutants having the amino acid sequence shown in SEQ ID NO: 97 or 98; (38) Mutants comprising mutations A102C, I152C, T54C, S190I and V296L, and containing an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 97 or 98; (39) Mutants having the amino acid sequence shown in SEQ ID NO: 99 or 100; and (40) Mutants comprising mutants A102C, I152C, T54A, S190I and V296L, and having an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 99 or 100. The nucleic acid according to claim 6, selected from one of the following.

8. A mutant of the RSV F protein containing F1 polypeptide and F2 polypeptide, compared to the wild-type RSV F protein, exhibits the following characteristics (1) to (8): (1) Substitution of K or E at position 66 by I, L, M, F or V; (2) Substitution of N at position 67 by I; (3) Substitution of S at position 213 by P; (4) Substitution of S at position 215 by P; (5) Substitution of N at position 216 by P; (6) Substitution of I at position 217 by P, F, Y, or W; (7) Substitution of D at position 486 by Q, S, H, N, T, P, C, L, I, F, or W; and (8) Substitution of V at position 487 by Q, T, N, I, K, P, R, S, Y, D, F, L, H, or C A nucleic acid comprising a polynucleotide that codes for a mutant containing one or more of the following mutations.

9. The mutations in the mutant are as follows (1) to (3): (1) One of the following mutations: substitution of S at position 213 by P, substitution of S at position 215 by P, substitution of N at position 216 by P, and substitution of I at position 217 by P, F, Y, or W; (2) One of the following mutations: substitution of K or E at position 66 by I, L, M, F or V and substitution of N at position 67 by I; and (3) One of the following mutations: substitution of D at position 486 by Q, S, H, N, T, P, C, L, I, F, or W and substitution of V at position 487 by Q, T, N, I, K, P, R, S, Y, D, F, L, H, or C The nucleic acid according to claim 8, comprising:

10. The mutations in the mutant are as follows (1) to (13): (1) I217P, E66I and D486Q; (2) I217P, N67I and E487Q; (3) I217P, E66I and E487T; (4) S215P, N67I and E487Q; (5) S213P, N67I and E487Q; (6) S213P, E66I and E487T; (7) S213P, E66I and D486Q; (8) N216P, N67I and E487Q; (9) N216P, E66I and E487T; (10) N216P, E66I and D486Q; (11) A102C, I152C, S213P and E66I; (12) P101C, I152C, S213P and E66I; and (13) S213P and E66I A nucleic acid according to any one of claims 1 to 9, selected from one of the groups.

11. The aforementioned mutants are (1) to (30) below: (1) A mutant having the amino acid sequence shown in SEQ ID NO: 31 or 32; (2) Mutants comprising mutations N216P, E66I and D486Q, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 31 or 32; (3) Mutants having the amino acid sequence shown in SEQ ID NO: 33 or 34; (4) Mutants comprising mutants N216P, E66I, and E487T, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 33 or 34; (5) Mutants having the amino acid sequence shown in SEQ ID NO: 35 or 36; (6) Mutants comprising mutants N216P, N67I, and E487Q, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 35 or 36; (7) Mutants having the amino acid sequence shown in SEQ ID NO: 37 or 38; (8) Mutants comprising the mutations S213P, E66I, and D486Q, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 37 or 38; (9) Mutants having the amino acid sequence shown in SEQ ID NO: 39 or 40; (10) Mutants comprising the mutations S213P, E66I, and E487T, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 39 or 40; (11) Mutants having the amino acid sequence shown in SEQ ID NO: 41 or 42; (12) Mutants comprising mutations S213P, N67I and E487Q, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 41 or 42; (13) Mutants having the amino acid sequence shown in SEQ ID NO: 43 or 44; (14) Mutants comprising mutations S215P, N67I and E487Q, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 43 or 44; (15) Mutants having the amino acid sequence shown in SEQ ID NO: 45 or 46; (16) Mutants comprising mutations I217P, E66I, and E487T, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 45 or 46; (17) Mutants having the amino acid sequence shown in SEQ ID NO: 47 or 48; (18) Mutants comprising mutations I217P, N67I, and E487Q, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 47 or 48; (19) Mutants having the amino acid sequence shown in SEQ ID NO: 49 or 50; (20) Mutants comprising mutations I217P, E66I and D486Q, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 49 or 50; (21) Mutants having the amino acid sequence shown in SEQ ID NO: 51 or 52; (22) Mutants comprising mutations S213P, E66I and E487T, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 51 or 52; (23) Mutants having the amino acid sequence shown in Sequence ID No. 53 or 54; (24) Mutants comprising the mutations S213P, E66I, and D486Q, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 53 or 54; (25) Mutants having the amino acid sequence shown in SEQ ID NO: 55 or 56; (26) Mutants comprising mutations A102C, I152C, S213P and E66I, and having an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 55 or 56; (27) Mutants having the amino acid sequence shown in SEQ ID NO: 57 or 58; (28) Mutants comprising mutants P101C, I152C, S213P and E66I, and containing an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 57 or 58; (29) Mutants having the amino acid sequence shown in SEQ ID NO: 59 or 60; and (30) Mutants comprising mutations S213P and E66I, which have an amino acid sequence that is at least 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, or 99.5% identical to the amino acid sequence shown in Sequence ID No. 59 or 60. The nucleic acid according to claim 10, selected from one of the following.

12. The wild-type RSV is subtype A or subtype B; Preferably, the wild-type RSV is wild-type hRSV; Preferably, the wild-type hRSV is strain A2, Ontario, or Buenos Aires. The nucleic acid according to any one of claims 1 to 11.

13. The nucleic acid is RNA; preferably, the RNA is mRNA; more preferably, the mRNA includes at least one of a 5'-cap structure, a 5'-UTR, a 3'-UTR, and a poly(A) tail; Alternatively, the nucleic acid is DNA; preferably, the DNA can be transcribed into RNA. The nucleic acid according to any one of claims 1 to 12.

14. The DNA sequence corresponding to the 5'-UTR is shown in Sequence ID No. 209; And / or, the DNA sequence corresponding to the 3'-UTR is shown in Sequence ID No. 210; and / or the nucleotides constituting the poly(A) tail comprise at least 20, at least 40, at least 80, at least 100, or at least 120 A nucleotides; preferably the nucleotides constituting the poly(A) tail comprise at least 20, at least 40, at least 80, at least 100, or at least 120 consecutive A nucleotides; preferably the nucleotides constituting the poly(A) tail comprise one or more nucleotides other than A nucleotides; more preferably the DNA sequence corresponding to the poly(A) tail is shown in SEQ ID NO:

211. The nucleic acid according to claim 13.

15. A nucleic acid according to any one of claims 1 to 14, comprising a modified nucleotide, Preferably comprising a modified nucleoside; preferably, the modified nucleoside comprising at least one of modified uridine, modified cytidine, modified adenosine, and modified guanosine, a nucleic acid.

16. The nucleic acid according to any one of claims 1 to 15, comprising a polynucleotide encoding one or more mutants of the RSV F protein.

17. The nucleic acid according to any one of claims 1 to 16, further comprising a polynucleotide encoding a protein or polypeptide other than a mutant of the RSV F protein.

18. The nucleic acid according to any one of claims 1 to 17, further comprising one or more of the following: a polynucleotide encoding the transmembrane domain of the RSV F protein, a polynucleotide encoding the pep27 polypeptide, a polynucleotide encoding a signal peptide, and a polynucleotide encoding a trimerization domain.

19. A genetically engineered vector comprising the nucleic acid described in any one of claims 1 to 18, or a polynucleotide that can be transcribed onto the nucleic acid described in any one of claims 1 to 18.

20. A host cell comprising the gene-manipulated vector according to claim 19.

21. A mutant of the RSV F protein encoded by the nucleic acid described in any one of claims 1 to 18; Preferably, the mutant is a trimer.

22. A nucleic acid composition comprising a first nucleic acid which is the nucleic acid described in any one of claims 1 to 18, or a first genetically modified vector which is the genetically modified vector described in claim 19; Alternatively, a plurality of first nucleic acids which are nucleic acids according to any one of claims 1 to 18, or a plurality of first genetically modified vectors which are genetically modified vectors according to claim 19, wherein the plurality of first nucleic acids are independent of each other, or the plurality of first genetically modified vectors are independent of each other. A delivery carrier that includes this.

23. The nucleic acid composition further comprises a second nucleic acid comprising a polynucleotide encoding a protein or polypeptide other than a mutant of the RSV F protein, or a second vector comprising a polynucleotide encoding a protein or polypeptide other than a mutant of the RSV F protein; and / or the first nucleic acid and the second nucleic acid are RNA; more preferably, the first nucleic acid and the second nucleic acid are mRNA, according to claim 22.

24. The delivery carrier is a lipid nanoparticle (LNP), a cationic liposome, a cationic protein, or a lipopolyplex (LPP); Preferably, the delivery carrier is the following compound (IV): 【Chemistry 1】 (IV) [In the formula, L ３ and L ４ These are the same or different, and each is independently C1-C12 alkylene, C2-C12 alkenylene, or C2-C12 alkynylene; preferably L ３ and L ４ These are the same or different, and each is independently C3-C10 alkylene, C3-C10 alkenylene, or C3-C10 alkynylene; more preferably, L ３ and L ４ They are the same or different, and each is independently a C3-C10 alkylene; most preferably L ３ and L ４ They are either the same or different, and each is independently a C5-C8 alkylene; G ４ and G ５ are the same or different and each independently is —O—(C═O)—, —(C═O)—O—, —C(═O)—, —O—, —C(═O)—S— or —S—C(═O)—; preferably, G ４ and G ５ are the same or different and each independently is —O—(C═O)—, —(C═O)—O—, —C(═O)— or —O—; most preferably, G ４ and G ５ are the same or different and each independently is selected from —O—(C═O)— or —(C═O)—O—; R １８ and R １９ They are the same or different, and each is independently a C5-C27 alkyl or C5-C27 alkenyl having one or more double bonds; preferably, R １８ and R １９ They are the same or different, and each is independently a C8-C20 alkyl or C8-C20 alkenyl having one or more double bonds; more preferably, R １８ and R １９ They are the same or different, each independently having one or two double bonds, a C9-C17 alkyl or C9-C18 alkenyl; most preferably, R １８ and R １９ They are either the same or different, and each is independent of the others. 【Chemistry 2】 And; R ２０ is a halogen, hydroxyl, cyano, C1-C6 alkyl, nitro, C1-C6 alkoxy, C1-C6 alkylcarbonyloxy, C1-C6 alkoxycarbonyl, C1-C6 alkylaminocarbonyl, or C1-C6 alkylcarbonylamino; preferably, R ２０ is a halogen, hydroxyl, cyano, C1-C6 alkoxy, C1-C6 alkylcarbonyloxy, C1-C6 alkoxycarbonyl, C1-C6 alkylaminocarbonyl, or C1-C6 alkylcarbonylamino; more preferably, R ２０ is a halogen, hydroxyl, cyano, C1-C4 alkoxy, C1-C4 alkylcarbonyloxy, C1-C4 alkoxycarbonyl, C1-C4 alkylaminocarbonyl or C1-C4 alkylcarbonylamino; most preferably, R ２０ is fluorine, hydroxyl, cyano, methoxy, acetoxy, methoxycarbonyl, butylaminocarbonyl, or acetamide; z is 1, 2, or 3. The delivery carrier according to claim 22 or 23, comprising lipid nanoparticles containing a cationic lipid, or a pharmaceutically acceptable salt or stereoisomer thereof.

25. The cationic lipid is the following compound (IV-1), or a pharmaceutically acceptable salt or stereoisomer thereof: 【Transformation 3】 And; Alternatively, the cationic lipid may be one of the following compounds, or a pharmaceutically acceptable salt thereof: 【Chemistry 4】 The delivery carrier according to claim 24.

26. A pharmaceutical composition comprising a nucleic acid according to any one of claims 1 to 18, a genetically modified vector according to claim 19, a host cell according to claim 20, a mutant of the RSV F protein according to claim 21, or a delivery carrier according to any one of claims 22 to 25, and a pharmaceutically acceptable carrier.

27. Including multiple delivery carriers; or the pharmaceutical composition according to claim 26, comprising a plurality of the nucleic acids.

28. The use of a nucleic acid according to any one of claims 1 to 18, a genetically modified vector according to claim 19, a host cell according to claim 20, a mutant of the RSV F protein according to claim 21, a delivery carrier according to any one of claims 22 to 25, or a pharmaceutical composition according to claim 26 or 27 in the preparation of a pharmaceutical product; Preferably, the pharmaceutical product is used for the prevention or treatment of RSV infection or disease caused by RSV infection; Preferably, the drug is a vaccine.

29. A vaccine comprising a nucleic acid according to any one of claims 1 to 18, a genetically modified vector according to claim 19, a mutant of the RSV F protein according to claim 21, or a delivery carrier according to any one of claims 22 to 25.

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