US 11,723,968 B2 · Stabilized recombinant hantaviral spike proteins comprising mutations in Gc

Abstract

The present invention describes specific engineering of the hantavirus spike proteins with modifications to stabilize (Gn/Gc)n heterodimer contacts and/or Gc homodimer contacts and/or Gn/Gn oligomer contacts on the spike with the purpose of using them as immunogens in next-generation vaccine design. Said spike proteins have been covalently stabilized by at least one disulphide inter-chain bond between Gn/Gc heterodimers and/or between Gc homodimers and/or between Gn homo-oligomers as they are presented at the surface of infectious virions. It also involves spike stabilization by introduction of cavity-filling amino acids with a bulky side chain at the above-mentioned contacts. Said spike proteins can be soluble Gn/Gc ectodomains in solution and/or incorporated as (Gn/Gc)n hetero-oligomers onto virus-like particles (VLPs) and/or used for pseudotyping virus vectors and/or form part of a stabilized recombinant virus, wherein said spike proteins can be used to select ligands and/or can be used for preventing or treating infections by one or more hantaviruses.

Claims14

Dependent claims

A stabilized hantaviral spike comprising at least one homodimer of Gc mutants, the at least one homodimer of Gc mutants comprising first and second polypeptide chains, each of the first and second polypeptide chains having an amino acid sequence that comprises the amino acid sequence of the Gc of SEQ ID NO:

1 at positions 652-1138 but with at least one amino acid substitution at a position determined when each of the first and second polypeptide chains is aligned with the Gc of SEQ ID NO:
1, wherein the at least one amino acid substitution in each of the first and second polypeptide chains is selected from the group consisting of:
the substitution G838C that results in the Gc mutant sequence of SEQ ID NO:
2, the substitution T839C that results in the Gc mutant sequence of SEQ ID NO:
3, the substitution H953C that results in the Gc mutant sequence of SEQ ID NO:
4, and the substitution H953F that results in the Gc mutant sequence of SEQ ID NO:
5.

4 more elements

Dependencies are inferred from the claim text.

Stabilized recombinant hantaviral spike proteins comprising mutations in Gc

Life of this patent

Stabilized recombinant hantaviral spike proteins comprising mutations in Gc

Life of this patent

Abstract

Claims14