FIELD: biotechnology.
SUBSTANCE: self-assembled icosahedral protein nanostructure for displaying influenza virus HA antigens is described. The nanostructure contains 20 trimeric assemblies. Each assembly has 3-order symmetry, with each trimeric assembly containing 3 trimer proteins. Each trimer protein contains a polypeptide consisting of the following (in order from N- to C-terminus): an extracellular influenza HA domain, a polypeptide linker, and a trimer subunit containing a polypeptide containing a sequence that is at least 95% identical to the amino acid sequence selected from the following SEQ ID NO: 7 or 29-31. The nanostructure also contains 12 pentameric assemblies with 5th order symmetry. Each pentameric assembly contains 5 pentamer subunits, where each pentamer subunit contains a polypeptide containing an amino acid sequence that is at least 95% identical to the amino acid sequence selected from the following SEQ ID NO: 8 or 32-34. Trimeric assemblies and pentameric assemblies form an icosahedron. The extracellular domain of influenza HA contains an amino acid sequence that is at least 85% identical to the amino acid sequence of the following SEQ ID NO: 57. In addition, a vaccine for providing a neutralizing antibody response to influenza containing the specified nanostructure is described. A method of creating immunity to influenza in a subject is presented, comprising administering an effective amount of a nanostructure or vaccine. A pharmaceutical composition containing the specified vaccine and a pharmaceutically acceptable adjuvant is also presented.
EFFECT: invention expands the arsenal of agents for treating influenza.
19 cl, 11 dwg, 4 tbl, 3 ex
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Authors
Dates
2024-01-11—Published
2019-02-28—Filed