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EP-4736871-A1 - RESPIRATORY SYNCYTIAL VIRUS (RSV) VACCINE

EP4736871A1EP 4736871 A1EP4736871 A1EP 4736871A1EP-4736871-A1

Abstract

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

Inventors

  • Li, Linxian
  • LI, HUI

Assignees

  • Shenzhen Shenxin Biotechnology Co., Ltd.

Dates

Publication Date
20260506
Application Date
20240621

Claims (20)

  1. A nucleic acid comprising a polynucleotide encoding a mutant of RSV F protein comprising an F1 polypeptide and an F2 polypeptide, and comprising, as compared to a wild-type RSV F protein, one or more of the following mutations: disulfide bond mutations, cavity filling mutation and electrostatic mutation.
  2. The nucleic acid according to claim 1, wherein the disulfide bond mutations comprise one or more of the 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, P101C 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 disulfide bond mutations comprise one or more of the follows: 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 nucleic acid according to any one of claims 1-2, wherein the cavity filling mutation comprises one or more of the following (1) to (3): (1) the substitution of T at position 54 by F, W, V, C, A, H, I, Y, L or M; preferably, the substitution of T at position 54 by F, W or V; (2) the 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) the substitution of V at position 296 by I, L, Y, H, F, or M.
  4. The nucleic acid according to any one of claims 1-3, wherein the electrostatic mutation comprises one or more of the follows: (1) the substitution of D at position 486 by Q, S, H, N, T, P, C, L, I, F, or W; and (2) the substitution of V at position 487 by Q, T, N, I, K, P, R, S, Y, D, F, L, H, or C.
  5. The nucleic acid according to any one of claims 1-4, wherein the mutations of the mutant comprise disulfide bond mutations and at least one of cavity filling mutation and electrostatic mutation; preferably, the mutations of the mutant comprise cavity filling mutation and disulfide bond mutations.
  6. The nucleic acid according to any one of claims 1-5, wherein the mutations of the mutant are selected from the following (1) to (20): (1) A102C, 1152C, T54V, S190M and V296L; (2) A102C, 1152C, T54F, S190M and V296L; (3) A102C, 1152C, T54C, S190M and V296L; (4) A102C, 1152C, T54A, S190M and V296L; (5) A102C, I152C, T54V, S190F and V296L; (6) A102C, I152C, T54F, S190F and V296L; (7) A102C, 1152C, T54C, S190F and V296L; (8) A102C, 1152C, T54A, S190F and V296L; (9) P101C, 1152C, T54V, S190M and V296L; (10) P101C, 1152C, T54F, S190M and V296L; (11) P101C, 1152C, T54C, S190M and V296L; (12) P101C, 1152C, T54A, S190M and V296L; (13) P101C, I152C, T54V, S190F and V296L; (14) P101C, 1152C, T54F, S190F and V296L; (15) P101C, I152C, T54C, S190F and V296L; (16) P101C, I152C, T54A, S190F and V296L; (17) A102C, 1152C, T54V, S190I and V296L; (18) A102C, 1152C, T54F, S190I and V296L; (19) A102C, 1152C, T54C, S190I and V296L; and (20) A102C, 1152C, T54A, S190I and V296L.
  7. The nucleic acid according to claim 6, wherein the mutant is selected from one of the following (1) to (40): (1) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 61 or 62; (2) a mutant comprising mutations A102C, I152C, T54V, S190M and V296L and comprising an amino acid sequence 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 as shown in SEQ ID NO: 61 or 62; (3) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 63 or 64; (4) a mutant comprising mutations A102C, I152C, T54F, S190M and V296L and comprising an amino acid sequence 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 as shown in SEQ ID NO: 63 or 64; (5) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 65 or 66; (6) a mutant comprising mutations A102C, I152C, T54C, S190M and V296L and comprising an amino acid sequence 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 as shown in SEQ ID NO: 65 or 66; (7) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 67 or 68; (8) a mutant comprising mutations A102C, I152C, T54A, S190M and V296L and comprising an amino acid sequence 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 as shown in SEQ ID NO: 67 or 68; (9) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 69 or 70; (10) a mutant comprising mutations A102C, 1152C, T54V, S190F and V296L and comprising an amino acid sequence 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 as shown in SEQ ID NO: 69 or 70; (11) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 71 or 72; (12) a mutant comprising mutations A102C, 1152C, T54F, S190F and V296L and comprising an amino acid sequence 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 as shown in SEQ ID NO: 71 or 72; (13) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 73 or 74; (14) a mutant comprising mutations A102C, 1152C, T54C, S190F and V296L and comprising an amino acid sequence 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 as shown in SEQ ID NO: 73 or 74; (15) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 75 or 76; (16) a mutant comprising mutations A102C, 1152C, T54A, S190F and V296L and comprising an amino acid sequence 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 as shown in SEQ ID NO: 75 or 76; (17) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 77 or 78; (18) a mutant comprising mutations P101C, 1152C, T54V, S190M and V296L and comprising an amino acid sequence 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 as shown in SEQ ID NO: 77 or 78; (19) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 79 or 80; (20) a mutant comprising mutations P101C, 1152C, T54F, S190M and V296L and comprising an amino acid sequence 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 as shown in SEQ ID NO: 79 or 80; (21) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 81 or 82; (22) a mutant comprising mutations P101C, I152C, T54C, S190M and V296L and comprising an amino acid sequence 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 as shown in SEQ ID NO: 81 or 82; (23) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 83 or 84; (24) a mutant comprising mutations P101C, I152C, T54A, S190M and V296L and comprising an amino acid sequence 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 as shown in SEQ ID NO: 83 or 84; (25) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 85 or 86; (26) a mutant comprising mutations P101C, 1152C, T54V, S190F and V296L and comprising an amino acid sequence 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 as shown in SEQ ID NO: 85 or 86; (27) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 87 or 88; (28) a mutant comprising mutations P101C, 1152C, T54F, S190F and V296L and comprising an amino acid sequence 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 as shown in SEQ ID NO: 87 or 88; (29) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 89 or 90; (30) a mutant comprising mutations P101C, I152C, T54C, S190F and V296L and comprising an amino acid sequence 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 as shown in SEQ ID NO: 89 or 90; (31) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 91 or 92; (32) a mutant comprising mutations P101C, I152C, T54A, S190F and V296L and comprising an amino acid sequence 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 as shown in SEQ ID NO: 91 or 92; (33) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 93 or 94; (34) a mutant comprising mutations A102C, I152C, T54V, S190I and V296L and comprising an amino acid sequence 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 as shown in SEQ ID NO: 93 or 94; (35) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 95 or 96; (36) a mutant comprising mutations A102C, I152C, T54F, S190I and V296L and comprising an amino acid sequence 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 as shown in SEQ ID NO: 95 or 96; (37) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 97 or 98; (38) a mutant comprising mutations A102C, I152C, T54C, S190I and V296L and comprising an amino acid sequence 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 as shown in SEQ ID NO: 97 or 98; (39) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 99 or 100; and (40) a mutant comprising mutations A102C, I152C, T54A, S190I and V296L and comprising an amino acid sequence having 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 as shown in SEQ ID NO: 99 or 100.
  8. A nucleic acid, comprising a polynucleotide encoding a mutant of RSV F protein comprising an F1 polypeptide and an F2 polypeptide, and comprising, as compared to a wild-type RSV F protein, one or more mutations of the following (1) to (8): (1) the substitution of K or E at position 66 by I, L, M, F or V; (2) the substitution of N at position 67 by I; (3) the substitution of S at position 213 by P; (4) the substitution of S at position 215 by P; (5) the substitution of N at position 216 by P; (6) the substitution of I at position 217 by P, F, Y or W; (7) the substitution of D at position 486 by Q, S, H, N, T, P, C, L, I, F, or W; and (8) the substitution of V at position 487 by Q, T, N, I, K, P, R, S, Y, D, F, L, H, or C.
  9. The nucleic acid according to claim 8, wherein the mutations of the mutant comprise the following (1) to (3): (1) one of the following mutations: the substitution of S at position 213 by P, the substitution of S at position 215 by P, the substitution of N at position 216 by P, and the substitution of I at position 217 by P, F, Y or W; (2) one of the following mutations: the substitution of K or E at position 66 by I, L, M, F or V and the substitution of N at position 67 by I; and (3) one of the following mutations: the substitution of D at position 486 by Q, S, H, N, T, P, C, L, I, F or W and the substitution of V at position 487 by Q, T, N, I, K, P, R, S, Y, D, F, L, H or C.
  10. The nucleic acid according to any one of claims 1-9, wherein the mutations of the mutant are selected from one group of the following (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, 1152C, S213P and E66I; (12) P101C, I152C, S213P and E66I; and (13) S213P and E66I.
  11. The nucleic acid according to claim 10, wherein the mutant is selected from one of the following (1) to (30): (1) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 31 or 32; (2) a mutant comprising mutations N216P, E66I and D486Q and comprising an amino acid sequence 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 as shown in SEQ ID NO: 31 or 32; (3) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 33 or 34; (4) a mutant comprising mutations N216P, E66I, and E487T and comprising an amino acid sequence 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 as shown in SEQ ID NO: 33 or 34; (5) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 35 or 36; (6) a mutant comprising mutations N216P, N67I, and E487Q and comprising an amino acid sequence 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 as shown in SEQ ID NO: 35 or 36; (7) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 37 or 38; (8) a mutant comprising mutations S213P, E66I, and D486Q and comprising an amino acid sequence 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 as shown in SEQ ID NO: 37 or 38; (9) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 39 or 40; (10) a mutant comprising mutations S213P, E66I, and E487T and comprising an amino acid sequence 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 as shown in SEQ ID NO: 39 or 40; (11) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 41 or 42; (12) a mutant comprising mutations S213P, N67I and E487Q and comprising an amino acid sequence 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 as shown in SEQ ID NO: 41 or 42; (13) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 43 or 44; (14) a mutant comprising mutations S215P, N67I and E487Q and comprising an amino acid sequence 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 as shown in SEQ ID NO: 43or 44; (15) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 45 or 46; (16) a mutant comprising mutations I217P, E66I, and E487T and comprising an amino acid sequence 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 as shown in SEQ ID NO: 45 or 46; (17) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 47 or 48; (18) a mutant comprising mutations I217P, N67I, and E487Q and comprising an amino acid sequence 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 as shown in SEQ ID NO: 47 or 48; (19) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 49 or 50; (20) a mutant comprising mutations I217P, E66I and D486Q and comprising an amino acid sequence 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 as shown in SEQ ID NO: 49 or 50; (21) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 51 or 52; (22) a mutant comprising mutations S213P, E66I and E487T and comprising an amino acid sequence 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 as shown in SEQ ID NO: 51 or 52; (23) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 53 or 54; (24) a mutant comprising mutations S213P, E66I, and D486Q and comprising an amino acid sequence 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 as shown in SEQ ID NO: 53 or 54; (25) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 55 or 56; (26) a mutant comprising mutations A102C, I152C, S213P and E66I and comprising an amino acid sequence 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 as shown in SEQ ID NO: 55or 56; (27) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 57 or 58; (28) a mutant comprising mutations P101C, I152C, S213P and E66I and comprising an amino acid sequence 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 as shown in SEQ ID NO: 57 or 58; (29) a mutant comprising the amino acid sequence as shown in SEQ ID NO: 59 or 60; and (30) a mutant comprising mutations S213P and E66I and comprising an amino acid sequence 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 as shown in SEQ ID NO: 59 or 60.
  12. The nucleic acid according to any one of claims 1-11, wherein 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, strain Ontario or strain Buenos Aires.
  13. The nucleic acid according to any one of claims 1-12, wherein the nucleic acid is RNA; preferably, the RNA is mRNA; more preferably, the mRNA comprises at least one of 5'-cap structure, 5'-UTR, 3'-UTR and poly(A) tail; or, the nucleic acid is DNA; preferably, the DNA can be transcribed into RNA.
  14. The nucleic acid according to claim 13, wherein the DNA sequence corresponding to the 5'-UTR is shown in SEQ ID NO: 209; and/or, the DNA sequence corresponding to the 3'-UTR is shown in SEQ 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 the A nucleotide; more preferably, the DNA sequence corresponding to the poly(A) tail is shown in SEQ ID NO: 211.
  15. The nucleic acid according to any one of claims 1-14, comprising a modified nucleotide; preferably, the nucleic acid comprises a modified nucleoside; preferably, the modified nucleoside comprises at least one of a modified uridine, a modified cytidine, a modified adenosine, and a modified guanosine.
  16. The nucleic acid of any one of claims 1-15, comprising a polynucleotide encoding one or more mutants of RSV F protein.
  17. The nucleic acid according to any one of claims 1-16, further comprising a polynucleotide encoding a protein or polypeptide other than the mutant of RSV F protein.
  18. The nucleic acid according to any one of claims 1-17, further comprising one or more of a polynucleotide encoding the transmembrane domain of RSV F protein, a polynucleotide encoding a pep27 polypeptide, a polynucleotide encoding a signal peptide, and a polynucleotide encoding a trimerization domain.
  19. A genetic engineering vector comprising the nucleic acid according to any one of claims 1-18, or a polynucleotide that can be transcribed into the nucleic acid according to any one of claims 1-18.
  20. A host cell comprising the genetic engineering vector of claim 19.

Description

Technical Field The present invention belongs to the field of biotechnology, and relates to a respiratory syncytial virus (RSV) vaccine. Background Respiratory syncytial virus (RSV) is a single-stranded RNA virus of Orthopneumovirus genus, Pneumoviridae. The genome of RSV includes 10 genes, which encode 11 proteins, including 9 structural proteins and 2 non-structural proteins, among which the structural proteins include 3 transmembrane surface glycoproteins: Attachment glycoprotein (G protein), Fusion protein (F protein) and small hydrophobic protein (SH protein). Human respiratory syncytial virus (human orthopneumovirus, hRSV) has two subtypes: subtype A and subtype B, which differ from each other mainly in G protein. The infection of hRSV may cause upper and lower respiratory tract diseases, has a high incidence in infants, immunocompromised people and elder people, is the second most common cause of infant death, and is also the main cause of illness and death in the elder people (> 60 years old). The fusion protein (F protein) is activated upon the cleavage into two fragments F1 and F2 by the host protease, which can cause the fusion of the virus capsule membrane and the host cell membrane, plays a role in the immunopathology caused by RSV infection, and is a popular protein in the research and development of antibodies, vaccines and other therapeutics. During the entry of RSV into cells, F protein is rearranged from a pre-fusion conformation to a post-fusion conformation through an intermediate extension structure. During the rearrangement, the C-terminal coiling helix of the pre-fusion molecule is disassociated into the three chains constituting the same, which are then coiled around the spherical head and conjugated to three additional helices to form a post-fusion six-helix bundle. To prevent the entry of virus, it is speculated that F-specific neutralizing antibodies have to bind to F on virions with the pre-fusion conformation, or potentially extended intermediates, before the viral envelope is fused to the cell membrane. Thus, the pre-fusion form of F protein (i.e., "pre-F protein") is considered as a preferred conformation for vaccine antigens. However, during the preparation of the pre-F protein, the pre-F protein is apt to convert into a fused form. Therefore, it is still a challenge to use the pre-F protein as a vaccine antigen. Summary The present disclosure provides a nucleic acid encoding a protein or polypeptide capable of inducing a specific immune response to prevent or at least reduce the infection of respiratory syncytial virus (RSV). In addition, the present disclosure also provides a delivery carrier, a pharmaceutical composition, an RSV vaccine and use thereof in the preparation of a medicament. A nucleic acid comprising a polynucleotide encoding a mutant of RSV F protein comprising an F1 polypeptide and an F2 polypeptide, and comprising, as compared to a wild-type RSV F protein, one or more of the following mutations: disulfide bond mutations, a cavity filling mutation and an electrostatic mutation. In some embodiments, the disulfide bond mutations comprise one or more of the 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, P101C 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. In some embodiments, the disulfide bond mutations comprise one or more of the follows: 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. In some embodiments, the cavity filling mutation includes one or more of the following (1) to (3): (1) the substitution of T at position 54 by F, W, V, C, A, H, I, Y, L or M; preferably, the substitution of T at position 54 by F, W or V;(2) the 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) the substitution of V at position 296 by I, L, Y, H, F, or M. In some embodiments, the electrostatic mutation includes one or more of the follows: (1) the substitution of D at position 486 by Q, S, H, N, T, P, C, L, I, F, or W; and(2) the substitution of V at position 487 by Q, T, N, I, K, P, R, S, Y, D, F, L, H, or C. In some embodiments, the mutations of the mutant include disulfide bond mutations and at least one of cavity filling mutation and electrostatic mutation; preferably, the mutations of the mutant include cavity filling mutation and disulfide bond mutations. In some embodiments, the mutations of the mutant are selected from one group of the following (1) to (20): (1)A102C, I152C, T54V, S190M and V296L; (2)A102C, I152C, T54F, S190M and V296L; (3)A102C, I152C, T54C, S190M and V296L; (4