Nucleic acid vaccine
Patent Information
- Application Number
- JP2026173751
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2014-12-08
- Filing Date
- 2026-07-16
- Publication Date
- 2026-10-22
AI Technical Summary
【0059】 前述の及び他の目的、特長及び利点は、添付の図面に示されるような本発明の具体的な 実施形態に関する以下の説明から明らかとなるであろう。図面では、それぞれの図を通じ て同一参照符号は同じ部分を指す。図面は必ずしも縮尺に従っておらず、むしろ本発明の 様々な実施形態の原理を図解することに重点が置かれている。
Smart Images
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Figure 2026170887000954
Abstract
Claims
1. It is a nucleic acid vaccine, and the open leading phrase codes for the antigenic polypeptide. Contains one or more RNA polynucleotides with a chromosome, and approximately 20-60% cationic lipids: Noncationic lipids 5-25%: Sterols approximately 25-55%: and PEG-modified lipids approximately 0.5% The nucleic acid vaccine is formulated within cationic lipid nanoparticles having a molar ratio of ~15%. 。
2. The cationic lipid nanoparticles include cationic lipids, PEG-modified lipids, sterols, and non- The vaccine according to claim 1, comprising a cationic lipid.
3. The cationic lipid is 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3 ]-Dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethyl Aminobutyrate (DLin-MC3-DMA) and di((Z)-non-2-ene-1- (L31) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioic acid (L31 The vaccine according to claim 2, selected from the group consisting of 9).
4. The cationic lipid nanoparticles consist of approximately 20-60% cationic lipids and approximately 20-60% non-cationic lipids. 5-25% sterol, approximately 25-55%, and PEG-modified lipids, approximately 0.5-15% molar ratio The vaccine according to claim 2 or 3, having the following characteristics.
5. The cationic lipid nanoparticles consist of approximately 50% cationic lipids and approximately 1.5% PE. G-modified lipids, containing approximately 38.5% cholesterol and approximately 10% noncationic lipids, please The vaccine described in item 2 or 3.
6. The cationic lipid nanoparticles consist of approximately 55% cationic lipids and approximately 2.5% PE. A claim comprising G lipids, approximately 32.5% cholesterol, and approximately 10% noncationic lipids. The vaccine described in 2 or 3.
7. The cationic lipid is an ionic cationic lipid, and the non-cationic lipid is neutral The vaccine according to claim 2, wherein the sterol is cholesterol.
8. The open reading frame is codon optimized, any one of claims 1 to 7 The vaccine described in item 1.
9. The antigenic polypeptide is induced from an infectious agent, as described in any one of claims 1 to 8. The vaccine.
10. The claim states that the infectious agent is selected from members of the group consisting of viral strains and bacterial strains. The vaccine described in section 9.
11. The aforementioned one or more RNA polynucleotides further code for an antigenic polypeptide. A vaccine as described in any one of the requests 1 to 8.
12. Claim that the one or more RNA polynucleotides include at least one chemical modification. The vaccines listed in 1-8.
13. The antigenic polypeptide is one of the proteins listed in Tables 6-14 and 29-30, The vaccine according to any one of claims 1 to 8, wherein the antigenic fragment is selected from thereto.
14. The open leading frames of the one or more RNA polynucleotides are shown in Tables 6-11. The antigenic polypeptide selected from Tables 22-23, or its antigenic fragment, is coded. The vaccine according to any one of claims 1 to 8.
15. The open reading frames of one or more RNA polynucleotides, A selection from any of the RNA sequences in Table 28 or an antigenic fragment thereof, according to claims 1 to 8. The vaccine listed in any one of the items.
16. The aforementioned infectious agent is influenza A, influenza B, or a combination thereof. The vaccine according to any one of claims 9 to 10, wherein the strain is a serotype.
17. The aforementioned strains of influenza A or influenza B are found in birds, pigs, horses, dogs, The vaccine according to claim 16, relating to humans or non-human primates.
18. The antigenic polypeptide codes for hemagglutinin protein or a fragment thereof. The vaccine according to any one of claims 1 to 16.
19. The hemagglutinin proteins are H1, H2, H3, H4, H5, H6, H7, H8 , H9, H10, H11, H12, H13, H14, H15, H16, H17, H18, The vaccine according to claim 18, or a fragment thereof.
20. Claim 18, wherein the hemagglutinin protein does not contain the head domain (HA1). Or the vaccine described in item 19.
21. Claim 18, wherein the hemagglutinin protein comprises a portion of the head domain (HA1). Or the vaccine described in item 19.
22. The hemagglutinin protein does not contain a cytoplasmic domain, according to claims 18 to 21. Either one of the vaccines listed in item 1.
23. The hemagglutinin protein comprises a portion of the cytoplasmic domain, according to claims 18-21. The vaccine listed in any one of the items.
24. Any of claims 18 to 23, wherein the hemagglutinin protein is of the truncated type. The vaccine described in item 1.
25. The claim states that the truncated hemagglutinin protein includes a portion of the transmembrane domain. A vaccine as described in any one of items 18 to 23.
26. The amino acid sequences of the hemagglutinin protein or its fragments are shown in Tables 14-16. Any of the amino acid sequences and at least 90%, 91%, 92%, 93%, 94%, 95% Any of claims 18 to 25, having identity of %, 96%, 97%, 98%, or 99% The vaccine described in item 1.
27. The aforementioned virus is selected from the group consisting of H1N1, H3N2, H7N9, and H10N8. The vaccine according to claim 18.
28. The antigenic polypeptide is one of the proteins listed in Tables 6-12 or a fragment thereof. The vaccine according to claim 18, selected from the above.
29. The vaccine according to any one of claims 1 to 28, wherein the nucleic acid vaccine is polyvalent.
30. The open reading frames of one or more RNA polynucleotides are at least The claim also codes for antigenic polypeptides 2, 3, 4, 5, 6, 7, 8, 9, or 10. The vaccine described in item 29.
31. The open reading frames of one or more RNA polynucleotides are at least The method according to claim 29, which codes for 10, 15, 20, or 50 antigenic polypeptides. vaccine.
32. The open reading frames of one or more RNA polynucleotides are 2 to 10 , antigenicity points 10-15, 15-20, 20-50, 50-100 or 100-200 The vaccine according to claim 29, which codes for a lipeptide.
33. The RNA polynucleotide includes chemical modifications, and the chemical modifications are as shown in Tables 22 and 23. A frame according to any one of claims 1 to 32, selected from any of the enumerated ones. Ding.
34. The aforementioned chemical modifications are pseudouridine, N1-methylpsuduridine, and 2-thiouridine. n, 4'-thiouridine, 5-methylcytosine, 2-thio-1-methyl-1-deazacy Pseudouridine, 2-thio-1-methyl-pseuduridine, 2-thio-5-aza-uri Zin, 2-thiodihydropsuduridine, 2-thiodihydrouridine, 2-thio Pseudouridine, 4-methoxy-2-thiopsuduridine, 4-methoxy-psud Uridine, 4-thio-1-methyl-psuduridine, 4-thio-psuduridine, 5 -Aza-uridine, dihydropsuduridine, 5-methoxyuridine and 2'-O-me The vaccine according to claim 33, selected from the group consisting of chiluridine.
35. Further comprising a second chemical modification, wherein the second chemical modification is one of those listed in Tables 22 and 23. The vaccine according to claim 34, selected from any of the following.
36. The combination of the first and second chemical modifications is selected from those listed in Table 25. The vaccine according to claim 35.
37. A nucleic acid vaccine, which codes for the first antigenic polypeptide using open-leading It contains one or more RNA polynucleotides having a frame, and is formulated inside nanoparticles. The vaccine wherein the nanoparticles have an average diameter of 50 to 200 nm.
38. The vaccine according to claim 37, wherein the nanoparticles have a polydispersity value of less than 0.
4.
39. The effective charge of the nanoparticles has a neutral net charge at a neutral pH, as described in claim 37. The vaccine.
40. The vaccine according to claim 37, wherein the nanoparticles have an average diameter of 80 to 100 nm.
41. The aforementioned nanoparticles are cationic lipids, PEG-modified lipids, sterols, and non-cationic lipids. The vaccine according to claim 37, wherein the cationic lipid nanoparticles contain the cationic lipid nanoparticles.
42. The cationic lipid is 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3 ]-Dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethyl Aminobutyrate (DLin-MC3-DMA) and di((Z)-non-2-ene-1- (L31) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioic acid (L31 The vaccine according to claim 41, selected from the group consisting of 9).
43. A nucleic acid vaccine, which codes for the first antigenic polypeptide using open-leading It comprises one or more RNA polynucleotides having a frame, and the open reading frame The vaccine wherein at least 80% of the uracil in the frame is chemically modified.
44. Claim that 100% of the uracil in the open reading frame is chemically modified. The vaccine described in item 43.
45. The vaccine according to claim 43 or 44, wherein the chemical modification is located at the 5-position of uracil.
46. Any one of claims 43 to 44, wherein the chemical modification is N1-methylpsuduridine. The vaccines listed in the section.
47. Claim 43, formulated within a cationic lipid complex or cationic lipid nanoparticles The vaccine described in any one of the items in section 46.
48. A nucleic acid vaccine, which codes for the first antigenic polypeptide using open-leading A frame having at least one 5'-terminated cap and at least one chemical modification Containing more than one RNA polynucleotide, formulated within cationic lipid nanoparticles, The aforementioned vaccine.
49. Claim 4, wherein the 5' end cap is 7mG(5')ppp(5')NlmpNp The vaccine described in item 8.
50. Claim that the chemical modification is selected from any of those listed in Tables 22 and 23. A vaccine as described in any one of items 48 to 49.
51. The aforementioned chemical modifications are pseudouridine, N1-methylpsuduridine, and 2-thiouridine. n, 4'-thiouridine, 5-methylcytosine, 2-thio-1-methyl-1-deazacy Pseudouridine, 2-thio-1-methyl-pseuduridine, 2-thio-5-aza-uri Zin, 2-thiodihydropsuduridine, 2-thiodihydrouridine, 2-thio Pseudouridine, 4-methoxy-2-thiopsuduridine, 4-methoxy-psud Uridine, 4-thio-1-methyl-psuduridine, 4-thio-psuduridine, 5 -Aza-uridine, dihydropsuduridine, 5-methoxyuridine and 2'-O-me The vaccine according to claim 50, selected from the group consisting of chiluridine.
52. Further comprising a second chemical modification, wherein the second chemical modification is one of those listed in Tables 22 and 23. The vaccine according to claim 50, selected from any of the following.
53. The combination of the first and second chemical modifications is selected from those listed in Table 25. The vaccine according to claim 52.
54. The cationic lipid nanoparticles include cationic lipids, PEG-modified lipids, sterols, and non- The vaccine according to claim 48, comprising a cationic lipid.
55. The cationic lipid is 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3 ]-Dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethyl Aminobutyrate (DLin-MC3-DMA) and di((Z)-non-2-ene-1- (L31) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioic acid (L31 The vaccine according to claim 54, selected from the group consisting of 9).
56. The cationic lipid nanoparticles consist of approximately 20-60% cationic lipids and approximately 20-60% non-cationic lipids. 5-25% sterol, approximately 25-55%, and PEG-modified lipids, approximately 0.5-15% molar ratio The vaccine according to claim 54 or 55, having the following characteristics.
57. It is a nucleic acid vaccine, and it is an open-reading nucleic acid that codes for hemagglutinin protein. One or more RNA polynucleotides having a frame and a pharmaceutically acceptable carrier or The vaccine, comprising an excipient and formulated within cationic lipid nanoparticles.
58. The hemagglutinin protein is selected from HA1, HA7, and HA10, according to the claim. The vaccine described in item 57.
59. The RNA polynucleotide does not code for the F protein, according to claim 57 or 58. The vaccines listed.
60. The RNA polynucleotide further codes for a neuraminidase protein, claim A vaccine as described in any one of items 57 to 59.
61. The hemagglutinin protein is a type of influenza A virus or influenza Any of claims 57 to 60, derived from a strain of type B virus or a combination thereof The vaccine described in item 1.
62. The influenza virus is selected from H1N1, H3N2, H7N9, and H10N8. The vaccine according to claim 61, which is selected.
63. The RNA polynucleotides include chemical modifications, and these chemical modifications are listed in Tables 22 and 23. A frame according to any one of claims 57 to 62, selected from any of those listed. Ding.
64. The aforementioned chemical modifications are pseudouridine, N1-methylpsuduridine, and 2-thiouridine. n, 4'-thiouridine, 5-methylcytosine, 2-thio-1-methyl-1-deazacy Pseudouridine, 2-thio-1-methyl-pseuduridine, 2-thio-5-aza-uri Zin, 2-thiodihydropsuduridine, 2-thiodihydrouridine, 2-thio Pseudouridine, 4-methoxy-2-thiopsuduridine, 4-methoxy-psud Uridine, 4-thio-1-methyl-psuduridine, 4-thio-psuduridine, 5 -Aza-uridine, dihydropsuduridine, 5-methoxyuridine and 2'-O-me The vaccine according to claim 63, selected from the group consisting of chiluridine.
65. Further comprising a second chemical modification, wherein the second chemical modification is one of those listed in Tables 22 and 23. The vaccine according to claim 63, selected from any of the following.
66. The combination of the first and second chemical modifications is selected from those listed in Table 25. The vaccine according to claim 65.
67. The cationic lipid nanoparticles include cationic lipids, PEG-modified lipids, sterols, and non- The vaccine according to claim 57, comprising a cationic lipid.
68. The cationic lipid is 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3 ]-Dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethyl Aminobutyrate (DLin-MC3-DMA) and di((Z)-non-2-ene-1- (L31) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioic acid (L31 The vaccine according to claim 67, selected from the group consisting of 9).
69. The cationic lipid nanoparticles consist of approximately 20-60% cationic lipids and approximately 20-60% non-cationic lipids. 5-25% sterol, approximately 25-55%, and PEG-modified lipids, approximately 0.5-15% molar ratio The vaccine according to claim 67 or 68, having the following characteristics.
70. The RNA polynucleotides comprising sequences 2459 to 2621, according to claims 57 to 69. Either one of the vaccines listed in item 1.
71. The RNA polynucleotides have at least 80% of the distribution of sequence numbers 2459-2621. It contains polynucleotides with column identity. The W of any one of claims 57 to 69 Kuching.
72. The RNA polynucleotide has at least 90% sequence identity with Sequence ID No. 2254. Any of claims 57 to 69, comprising a polynucleotide that codes for the amino acid sequence having The vaccine described in item 1.
73. The RNA polynucleotide is a polynucleotide that codes for the amino acid sequence of SEQ ID NO: 2254. A vaccine according to any one of claims 57 to 69, comprising a creotide.
74. The RNA polynucleotide has at least 90% sequence identity with Sequence ID No. 2259. Any of claims 57 to 69, comprising a polynucleotide that codes for the amino acid sequence having The vaccine described in item 1.
75. The RNA polynucleotides are polynucleotides that code for the amino acid sequence of SEQ ID NO: 2259. A vaccine according to any one of claims 57 to 69, comprising a creotide.
76. The RNA polynucleotide has at least 90% sequence identity with SEQ ID NO: 2192. Any of claims 57 to 69, comprising a polynucleotide that codes for the amino acid sequence having The vaccine described in item 1.
77. The RNA polynucleotides are polynucleotides that code for the amino acid sequence of SEQ ID NO: 2192. A vaccine according to any one of claims 57 to 69, comprising a creotide.
78. The RNA polynucleotide has at least 90% sequence identity with SEQ ID NO: 2200. Any of claims 57 to 69, comprising a polynucleotide that codes for the amino acid sequence having The vaccine described in item 1.
79. The RNA polynucleotides are polynucleotides that code the amino acid sequence of SEQ ID NO: 2200. A vaccine according to any one of claims 57 to 69, comprising a creotide.
80. Any of claims 57 to 69, wherein the RNA polynucleotide comprises SEQ ID NO: 2046 The vaccine described in item 1.
81. The RNA polynucleotide has 80-98% sequence identity with sequence number 2046. A vaccine according to any one of claims 57 to 69, comprising a polynucleotide.
82. Any of claims 57 to 69, wherein the RNA polynucleotide comprises Sequence ID No. 2119. The vaccine described in item 1.
83. The RNA polynucleotide has 80-98% sequence identity with SEQ ID NO: 2119. A vaccine according to any one of claims 57 to 69, comprising a polynucleotide.
84. Any of claims 57 to 69, wherein the RNA polynucleotide comprises Sequence ID No. 2054. The vaccine described in item 1.
85. The RNA polynucleotide has 80-98% sequence identity with SEQ ID NO: 2054. A vaccine according to any one of claims 57 to 69, comprising a polynucleotide.
86. Any of claims 57 to 69, wherein the RNA polynucleotide includes Sequence ID No. 2127. The vaccine described in item 1.
87. The RNA polynucleotide has 80-98% sequence identity with SEQ ID NO: 2127. A vaccine according to any one of claims 57 to 69, comprising a polynucleotide.
88. Nucleic acids containing 80-95% sequence identity with sequence number 2127 or sequence number 2054.
89. Nucleic acid containing sequence number 2624.
90. A method for inducing an antigen-specific immune response in a target, any one of claims 1 to 89 Administer the vaccine described in item 1 to the target in an effective dose to induce an antigen-specific immune response. The method, including the above.
91. The method according to claim 90, wherein the antigen-specific immune response includes a T cell response.
92. The method according to claim 90, wherein the antigen-specific immune response includes a B-cell response.
93. Claim 9, wherein the method for inducing an antigen-specific immune response involves a single dose of vaccine. The method described in 0.
94. The method according to claim 90, further comprising administering a booster dose of the vaccine.
95. The vaccine is administered to the subject by intradermal injection or intramuscular injection, as described in claim 90. Method of loading.
96. Claims 1 to 89 for use in a method for inducing an antigen-specific immune response in a target A vaccine according to any one of the paragraphs, wherein the method involves administering the vaccine to a target in an effective amount. The vaccine comprises providing a substance that induces an antigen-specific immune response.
97. Manufacturing of drugs for use in methods that induce antigen-specific immune responses in a target. The use of the vaccine according to any one of claims 1 to 89, wherein the method is This includes administering the aforementioned vaccine to a target in an effective dose to induce an antigen-specific immune response. The aforementioned use.
98. An injection comprising administering the vaccine described in any one of claims 57 to 89 to the target of Methods for preventing or treating influenza virus infection.
99. The method according to claim 98, wherein the antigen-specific immune response includes a T cell response.
100. The method according to claim 98, wherein the antigen-specific immune response includes a B-cell response.
101. Claim 9, wherein the method for inducing an antigen-specific immune response involves a single dose of vaccine. The method described in 8.
102. The vaccine is administered to the subject by intradermal injection or intramuscular injection, as described in claim 98. Method of loading.
103. Claim 5 for use in a method for preventing or treating influenza virus infection A vaccine according to any one of paragraphs 7 to 89, wherein the method involves applying the vaccine to a target. The vaccine, including administration.
104. Manufacturing of drugs for use in the prevention or treatment of influenza virus infection The use of the vaccine according to any one of claims 57 to 89 in the manufacture, the method The Act includes the use of the vaccine, which includes administering the vaccine to the subject.
105. One or more open leading frames that code the first antigenic polypeptide This includes administering nucleic acid vaccines containing the above RNA polynucleotides to the target. A vaccination method wherein the RNA polynucleotide does not contain stabilizing elements, and furthermore, The method wherein uvant is not co-formulated with or co-administered with the vaccine.
106. A nucleic acid vaccine in doses of 10 ug / kg to 400 ug / kg is administered to the subject, claim The method described in item 105.
107. Claim 105, wherein the nucleic acid is administered to the subject by intradermal injection or intramuscular injection. Method of description.
108. The method according to claim 105, wherein the nucleic acid is administered to the subject on day 0.
109. Claim 108, wherein a second dose of the nucleic acid vaccine is administered to the subject on the 21st day. Method of description.
110. The nucleic acid vaccine administered to the subject contains a dose of 25 micrograms of RNA polynucleotide. The method according to claim 105, comprising a rheotide.
111. The nucleic acid vaccine administered to the subject contains 100 micrograms of RNA polymerase The method according to claim 105, comprising a creotide.
112. The nucleic acid vaccine administered to the subject contains 400 micrograms of RNA polymerase The method according to claim 105, comprising a creotide.
113. The RNA polynucleotides are 10 times higher in local lymph nodes compared to distal lymph nodes. The method according to claim 105, which involves accumulating at a level 0 times higher.
114. A nucleic acid vaccine for use in a method of vaccinating a target, the aforementioned nucleic acid vaccine However, the first has an open leading frame that codes for the first antigenic polypeptide. It contains RNA polynucleotides, and the RNA polynucleotides do not contain stabilizing elements. Furthermore, the nucleic acid vaccine is characterized in that the adjuvant is not co-formulated with or co-administered with the vaccine.
115. Use of nucleic acid vaccines in the manufacture of drugs used for vaccination methods for the target population. The nucleic acid vaccine is an open lead that codes for a first antigenic polypeptide. The RNA polynucleotide comprises a first RNA polynucleotide having a wing frame, and the RNA polynucleotide The drug does not contain stabilizing elements, and furthermore, the adjuvant is not co-formulated with or co-administered with the vaccine. i, the aforementioned use.
116. Forming, maintaining, or modifying antigenic memory against influenza strains in individuals or populations. A method of restoration, wherein the individual or population (a) at least one RNA polynucleate Otide, having at least one chemical modification and two or more codon-optimized open The open leading frame comprises a series of reference antigenic points. (b) the polynucleotide coding the lipeptide, and (b) an optional pharmaceutically acceptable carrier. The method comprising administering an antigen memory booster nucleic acid vaccine, or an excipient. Law.
117. The aforementioned vaccine is administered via a route selected from the group consisting of intramuscular, intradermal, and subcutaneous administration. The method according to claim 116, wherein the substance is administered to the individual via the substance.
118. The administration step involves bringing the target muscle tissue into contact with a device suitable for injecting the composition. The method according to claim 117, which includes the action of
119. The administration step involves using electroporation to deliver the composition to muscle tissue. The method according to claim 117, comprising bringing it into contact with a device suitable for shooting.
120. Forming, maintaining, or modifying antigenic memory against influenza strains in individuals or populations. An antigen memory booster nucleic acid vaccine for use in a recovery method, wherein the antigen memory booster -Star-Nucleic acid vaccines (a) are at least one RNA polynucleotide, At least one chemical modification and two or more codon-optimized open leading phrases The open leading frame includes a series of reference antigenic polypeptides. (b) the polynucleotide and (b) optionally a pharmaceutically acceptable carrier or excipient. The method further includes administering the antigen memory booster nucleic acid vaccine to the individual or population. The antigen memory booster nucleic acid vaccine, including the administration of the above.
121. Forming, maintaining, or modifying antigenic memory against influenza strains in individuals or populations. The use of antigen memory booster nucleic acid vaccines in the manufacture of drugs for use in recovery methods The use is such that the antigen memory booster nucleic acid vaccine (a) contains at least one RNA A renucleotide having at least one chemical modification and two or more codon-optimized Includes an open reading frame, the open reading frame is a series of references (b) a polynucleotide that codes for an antigenic polypeptide, and (b) optionally a pharmaceutically acceptable The method further comprises a carrier or excipient, wherein the individual or population has the antigen memory The use described above includes administering a booster nucleic acid vaccine.
122. A nucleic acid vaccine for use in a method of vaccinating a target, the aforementioned nucleic acid vaccine The first has an open leading frame that codes for the first antigenic polypeptide. The method further comprises RNA polynucleotides, and the nucleic acid vaccine is a single dose of 25 ug The subject is vaccinated by administering an effective dose of 400 uG / kg to 400 uG / kg to the subject. The nucleic acid vaccine, including the above.
123. Use of nucleic acid vaccines in the manufacture of drugs used for vaccination methods for the target population. The nucleic acid vaccine is an open-ready nucleotide that codes for a first antigenic polypeptide. The method comprises a first RNA polynucleotide having a ng frame, and further the nucleic acid A single dose of the vaccine, ranging from 25 ug / kg to 400 ug / kg, is administered to the subject in an effective dose. The use includes vaccinating the subject.
124. It is a nucleic acid vaccine, and it is an open-ready vaccine that codes for hemagglutinin protein fragments. It comprises one or more RNA polynucleotides having a ng frame, and the hemagglutinin Of the head domain (HA1), cytoplasmic domain, or transmembrane domain, the protein is less The nucleic acid vaccine, which contains at least one part of a nucleic acid.
125. The hemagglutinin proteins are H1, H2, H3, H4, H5, H6, H7, H8 , H9, H10, H11, H12, H13, H14, H15, H16, H17, H18 A vaccine according to claim 124.
126. Claim 124, wherein the hemagglutinin protein does not contain the head domain (HA1). The vaccines listed.
127. The hemagglutinin protein described in claim 124 is characterized by not containing a cytoplasmic domain. vaccine.
128. The claim states that the truncated hemagglutinin protein does not contain a transmembrane domain. A vaccine as described in any one of items 124 to 127.
129. The amino acid sequence of the hemagglutinin protein is one of the amino acid sequences shown in 14-16. The difference is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%. The invention described in any one of claims 124 to 128, having 98% or 99% identity. The vaccine.
130. The vaccine is formulated within a cationic lipid complex or cationic lipid nanoparticles. The vaccine according to any one of claims 124 to 129.
131. The polynucleotide comprises at least one 5′ terminal cap and at least one nucleotide A vaccine according to any one of claims 124 to 130, including chemical modification.