Mutant of RSV F protein and application thereof

By introducing specific amino acid mutations into the RSV F protein, the expression and stability of the pre-fusion conformation and the trimer conformation were improved, which solved the problem of instability of the F protein in RSV vaccines, enhanced the induction ability of neutralizing antibodies, and improved the immunization effect of the vaccine.

CN122444831APending Publication Date: 2026-07-24BEIJING NEOCURNA BIOTECHNOLOGY CORP
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Patent Information

Application Number
CN202511753841.4
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Priority Date
2025-01-24
Filing Date
2025-11-26
Publication Date
2026-07-24

AI Technical Summary

Technical Problem

Existing RSV vaccines lack an effective protective immune response, and the pre-fusion conformation of the F protein is unstable, making it difficult to maintain key neutralizing epitopes, which poses challenges to vaccine development.

Method used

By introducing mutations at specific amino acid positions in the RSV F protein, such as amino acid substitutions at positions 176 and 186, the introduction of disulfide bonds, cavity filling, and electrostatic mutations, the expression and stability of the pre-fusion conformation and the trimer conformation can be improved.

Benefits of technology

It significantly improved the expression level and stability of the pre-fusion and trimer conformations of the F protein, enhanced the induction ability of neutralizing antibodies, inhibited the transformation of the F protein to the post-fusion conformation, and improved the immunization effect of the vaccine.

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Abstract

The invention relates to a mutant of RSV F protein, said mutant comprising an amino acid mutation relative to the amino acid sequence of RSV wild-type F protein, said amino acid mutation comprising mutation from K to P, R, H, S, T, N, Q, V, I, L or M at position 176; and / or the 186 position is mutated from S to P, R, H, K, D, E, T, N, Q, C, A, V, I, L, M, F, Y, or W. The invention also provides a related DNA (deoxyribonucleic acid) coding sequence, a recombinant plasmid, an mRNA (messenger ribonucleic acid) sequence and a corresponding RSV vaccine. Specific amino acid substitution is introduced to a special amino acid site and is combined with cavity filling, electrostatic mutation, proline mutation and the like, so that the expression and the stability of the F protein with conformations before and after fusion and trimer conformations are remarkably improved, and the F protein is remarkably inhibited from being converted into conformations after fusion.
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