Nanoparticle-based influenza virus vaccines and uses thereof

A nanoparticle, comprising:

• (a) a plurality of first assemblies, each first assembly comprising a plurality of identical first proteins;
• and,
• (b) a plurality of second assemblies, each second assembly comprising a plurality of second proteins;
• wherein at least one second assembly comprises at least one second protein joined to an immunogenic portion of an influenza hemagglutinin (HA) protein, thereby forming a fusion protein;
• wherein the sequence of the first protein differs from the sequence of the second protein;
• wherein the plurality of first assemblies non-covalently interact with the plurality of second assemblies to form the nanoparticle;
• and,
• wherein the nanoparticle displays the immunogenic portion of an HA protein on its surface;
• wherein the immunogenic portion comprises an influenza virus stabilized HA stem protein;
• and
• wherein the stabilized stem protein comprises an amino acid sequence at least 80%, 85%, 90%, 91%, 95%, 96%, 97%, 98%, 99%, or 100% identical, to an amino acid sequence corresponding to amino acids 1-58 of SEQ ID NO:
• 1, covalently joined, either directly or through a peptide linker, to an amino acid sequence at least 80%, 85%, 90%, 91%, 95%, 96%, 97%, 98%, or 99% identical, or 100% identical, to an amino acid sequence corresponding to amino acids 292-517 of SEQ ID NO:1, such that the stabilized stem protein lacks the amino acid sequence corresponding to amino acids 59-291 (SEQ ID NO:2).

A fusion protein comprising

• (a) an amino acid sequence at least 80%, 85%, 90%, 91%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO:89, SEQ ID NO:245, SEQ ID NO:247, SEQ ID NO:249, SEQ ID NO:251, SEQ ID NO:253, SEQ ID NO:255, and SEQ ID NO:257, joined to an immunogenic portion of an influenza virus HA protein;
• or
• (b) an amino acid sequence at least 80%, 85%, 90%, 91%, 95%, 96%, 97%, 98%, or 99% identical, or 100% identical to a sequence selected from the group consisting of SEQ ID NO:91, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO:101, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:107, SEQ ID NO:109, SEQ ID NO:111 SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:127, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:141, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:147, SEQ ID NO:149, SEQ ID NO:151, SEQ ID NO:153, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:177, SEQ ID NO:179, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:187, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:199, SEQ ID NO:201 SEQ ID NO:203, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211 SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:219, SEQ ID NO:221 SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:259, SEQ ID NO:261, SEQ ID NO:263, SEQ ID NO:265, and SEQ ID NOS:340-346.

A nanoparticle, comprising

• (a) a plurality of first assemblies, each first assembly comprising a plurality of identical first polypeptides comprising an amino acid sequence that is at least 80%, 85%, 90%, 91%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the full length of the amino acid sequence of any one of SEQ ID NOS:
• 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, and 87, wherein the polypeptide is not identical to the full length of the amino acid sequence of SEQ ID NO:
• 41, and,
• (b) a plurality of second assemblies, each second assembly comprising a plurality of second polypeptides;
• wherein the sequence of the first polypeptide differs from the sequence of the second polypeptide;
• and
• wherein the plurality of first assemblies non-covalently interact with the plurality of second assemblies to form the nanoparticle.