US 11,890,339 B2
Nipah virus immunogens and their use
Barney Graham, Rockville, MD (US); Rebecca Loomis, Bethesda, MD (US); Guillaume Stewart-Jones, Cambridge, MA (US); John Mascola, Rockville, MD (US); and Jason McLellan, Austin, TX (US)
Assigned to The United States of Americam as represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US); and Trustees of Dartmouth College, Hanover, NH (US)
Appl. No. 17/261,828
Filed by The United States of America, as represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US); and Trustees of Dartmouth College, Hanover, NH (US)
PCT Filed Aug. 5, 2019, PCT No. PCT/US2019/045110
§ 371(c)(1), (2) Date Jan. 20, 2021,
PCT Pub. No. WO2020/028902, PCT Pub. Date Feb. 6, 2020.
Claims priority of provisional application 62/714,230, filed on Aug. 3, 2018.
Prior Publication US 2021/0299242 A1, Sep. 30, 2021
Int. Cl. A61K 39/155 (2006.01); A61P 31/14 (2006.01); C07K 14/005 (2006.01); A61K 39/00 (2006.01)
CPC A61K 39/155 (2013.01) [A61P 31/14 (2018.01); C07K 14/005 (2013.01); A61K 2039/70 (2013.01); C07K 2319/03 (2013.01); C12N 2760/18222 (2013.01); C12N 2760/18223 (2013.01); C12N 2760/18234 (2013.01)] 35 Claims
 
1. An immunogen, comprising:
a recombinant Nipah virus (NiV) F ectodomain trimer stabilized in a prefusion conformation by one or more amino acid substitutions in protomers of the trimer, the amino acid substitutions comprising one or more of the following:
cysteine substitutions at NiV F positions 104 and 114 that form a non-natural intra-protomer disulfide bond, or cysteine substitutions at NiV F positions 114 and 426 that form a non-natural intra-protomer disulfide bond;
a proline substitution at NiV F position 191;
a phenylalanine substitution at NiV F position 172;
a glycine substitution at NiV F position 70; and
a deletion of NiV F positions 102-113 with positions 101 and 114 linked by a glycine-serine linker;
wherein the NiV F positions are according to the reference NiV F sequence set forth as SEQ ID NO: 52.