CN-122011209-A - Fusion protein and application thereof

Abstract

The invention discloses a fusion protein and application thereof. Belongs to the technical field of biological medicine. The invention provides a novel fusion molecular architecture, which comprises two genes encoding fusion proteins wza and hphA, and can be used for research and development of nucleic acid vaccines or subunit vaccines. The invention discovers that the novel fusion molecule has good expression secretion capacity and immunogenicity, can provide effective immune protection effect, and can obviously inhibit Acinetobacter baumannii infection and colonization. The invention also provides corresponding recombinant nucleic acid, gene expression cassette, vector, host cell, pharmaceutical composition, vaccine, use and the like.

Inventors

• YI XIANGUO
• HAN TIYUN
• XU SHI
• LIU SHANG
• LI ZHILI
• JIN XINXIN

Assignees

• 信阳农林学院

Dates

Publication Date

20260512

Application Date

20260203

Claims (10)

1. 1. A fusion protein comprising wza protein or an antigen-truncated fragment thereof, hphA protein or an antigen-truncated fragment thereof.
2. 2. The fusion protein of claim 1, wherein the fusion protein comprises wza antigen-truncated fragment, hphA antigen-truncated fragment; The wza antigen-truncated fragment is an N-terminal truncated, a C-terminal truncated, a transmembrane region truncated or an extracellular region fragment of wza protein, and is used for stimulating a specific immune response against wza antigen; The hphA antigen-truncated fragment is an N-terminal truncated, C-terminal truncated, or functional domain fragment of hphA protein for stimulating a specific immune response against the hphA antigen.
3. 3. The fusion protein of claim 2, wherein the wza antigen-truncated fragment has the amino acid sequence shown in SEQ ID No.1 and the hphA antigen-truncated fragment has the amino acid sequence shown in SEQ ID No. 2.
4. 4. The fusion protein of claim 2, wherein the wza antigen-truncated fragment and hphA antigen-truncated fragment are linked by a linker sequence.
5. 5. The fusion protein of claim 2, wherein the amino acid sequence is set forth in SEQ ID No. 4.
6. 6. A recombinant nucleic acid molecule encoding the fusion protein of any one of claims 1-5.
7. 7. A recombinant gene expression cassette comprising the recombinant nucleic acid molecule of claim 6.
8. 8. A recombinant vector comprising the recombinant gene expression cassette of claim 7.
9. 9. A recombinant host cell comprising the recombinant vector of claim 8.
10. 10. Use of the fusion protein according to any one of claims 1 to 5, the recombinant nucleic acid molecule according to claim 6, the recombinant gene expression cassette according to claim 7, the recombinant vector according to claim 8, and the recombinant host cell according to claim 9 for the preparation of a medicament for treating or preventing a disease caused by acinetobacter baumannii.

Description

Fusion protein and application thereof Technical Field The invention relates to the technical field of biological medicine, in particular to a fusion protein and application thereof. Background Acinetobacter baumannii (Acinetobacter baumannii) is a conditionally pathogenic gram-negative bacterium, widely existing in hospital environments, and is one of the important multi-drug resistant (MDR) pathogens causing nosocomial infections in recent years. The acinetobacter baumannii infection mainly causes ventilator-associated pneumonia, blood flow infection, meningitis, wound infection, urinary tract infection and the like, and the death rate of severe patients after infection can reach 30% -50%. Acinetobacter baumannii can rapidly colonize and invade the lungs of a host and the surfaces of medical instruments through a plurality of virulence factors such as capsular polysaccharide, outer membrane proteins, lipopolysaccharide, biofilm and the like. It has extremely strong environmental viability, can survive on dry surfaces for weeks or even months, and is transmitted through the formation of biofilms by ventilators, catheters and medical devices. The pathogen carries Multiple Drug Resistance (MDR) and even pan drug resistance (XDR) genes, and the drug resistance rate to final antibiotics such as carbapenems, polymyxins and the like is continuously increased, so that the clinical treatment failure rate is high, the hospitalization period is obviously prolonged, and the medical cost is sharply increased. Safe and effective vaccines are considered as strategic means to fundamentally prevent acinetobacter baumannii infection, reduce antibiotic use and suppress drug resistance transmission. Current vaccine development against acinetobacter baumannii is mainly focused on inactivated vaccines, recombinant protein vaccines, polysaccharide protein conjugate vaccines, and outer membrane vesicle vaccines. However, these vaccines have the problems of single antigen, weak immune response, limited protection range, and the like. In addition, the traditional inactivated vaccine has the defects of complex production and high risk of immune pathology, and limits the clinical application of the traditional inactivated vaccine. Thus, there is an urgent need to find new antigen targets, new antigen combinations or new vaccine preparation technologies for developing prophylactic or therapeutic vaccines against acinetobacter baumannii. Disclosure of Invention In view of this, the present invention provides a fusion protein and its use. Aiming at the problems, the invention provides a novel fusion protein design scheme, and aims to develop an efficient Acinetobacter baumannii infection prevention vaccine. In order to solve the technical problems, the invention adopts the following technical scheme: a fusion protein comprising wza protein or an antigen-truncated fragment thereof, hphA protein or an antigen-truncated fragment thereof. Further, the antigen is derived from a gram negative bacterium, preferably Acinetobacter baumannii (Acinetobacter baumannii). Further, the fusion protein comprises wza antigen-truncated fragment and hphA antigen-truncated fragment; The wza antigen-truncated fragment is an N-terminal truncated, a C-terminal truncated, a transmembrane region truncated or an extracellular region fragment of wza protein, and is used for stimulating a specific immune response against wza antigen; The hphA antigen-truncated fragment is an N-terminal truncated, C-terminal truncated, or functional domain fragment of hphA protein for stimulating a specific immune response against the hphA antigen. Further, the amino acid sequence of the wza antigen truncated fragment is shown as SEQ ID No.1, and the amino acid sequence of the hphA antigen truncated fragment is shown as SEQ ID No. 2. Further, the wza antigen truncated fragment and the hphA antigen truncated fragment are connected by a linker sequence. Further, the amino acid sequence of the linker sequence is shown as SEQ ID No. 3. Further, the amino acid sequence of the polypeptide is shown as SEQ ID No. 4. A recombinant nucleic acid molecule encoding the fusion protein. Further, the nucleotide sequence of the recombinant nucleic acid molecule is shown as SEQ ID No. 5. A recombinant gene expression cassette comprising the recombinant nucleic acid molecule described above. A recombinant vector comprising the recombinant gene expression cassette described above. A recombinant host cell comprising the recombinant vector described above. An immunogenic or pharmaceutical composition comprising the fusion protein described above, the recombinant nucleic acid molecule described above, the recombinant gene expression cassette described above, the recombinant vector described above, the recombinant host cell described above, preferably the immunogenic or pharmaceutical composition further comprises a pharmaceutically acceptable carrier. A recombinant vaccine comprising the fusion protein,