A Zika / dengue vaccine and its application

By introducing specific mutations in the E-protein fusion region of Zika/dengue virus, the problem of possible aggravation of dengue virus infection after vaccine immunity is solved, and the enhanced infection effect of reducing or eliminating antibody-dependent is achieved, and the immunogenicity of the antigen is maintained.

CN114907456BActive Publication Date: 2025-05-30INST OF MICROBIOLOGY CHINESE ACAD OF SCI
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Patent Information

Application Number
CN202210545896.6
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Priority Date
2019-11-07
Filing Date
2020-11-09
Publication Date
2025-05-30
Estimated Expiration
2040-11-09

AI Technical Summary

Technical Problem

The existing Zika/dengue vaccine designs have antibody-dependent infection enhancement (ADE) effects, which may aggravate dengue virus infection after vaccine immunity.

Method used

By introducing specific mutations in the E-protein fusion region of Zika or dengue virus, such as mutations at the D98, N103, G106, L107, F108 sites, a new antigen is designed to avoid binding to the antibodies causing the ADE, thereby reducing or eliminating the ADE effect.

Benefits of technology

The vaccine design can effectively avoid the production of FL epitope-induced antibodies, reduce or eliminate the ADE effect on dengue virus after immunization, while maintaining the immunogenicity of the antigen, and activate the production of neutralizing antibodies and provide protection.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention belongs to the field of biotechnology, and particularly relates to a Zika / dengue vaccine and its application. Based on crystal structure analysis and other structural and functional analyses, the present invention obtains the epitope information of the main antibody causing the ADE effect. The antigen provided in the present invention introduces mutations in the FL fusion region of the E protein of Zika virus or dengue virus, and antigens with such mutations cannot bind to the antibody causing ADE (FLE antibody); the vaccine provided by the present invention, after immunization, can avoid the production of antibodies induced by the FL epitope, thereby reducing or eliminating the ADE effect.
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Claims

1. An antigen, wherein the immunogenic portion of the antigen consists of the full-length E protein sequence of Zika virus or Dengue virus and the full-length M protein or full-length prM protein sequence of Zika virus or Dengue virus, wherein, the FL fusion region of the E protein has mutations, and the mutations in the FL fusion region of the E protein are selected from the following mutations or combinations of mutations: ； wherein: when the antigen includes the full-length E protein of Zika virus, the antigen further includes the full-length M protein or full-length prM protein sequence of Zika virus; when the antigen includes the full-length E protein of Dengue virus, the antigen further includes the full-length M protein or full-length prM protein sequence of Dengue virus.

2. A polynucleotide encoding the antigen according to claim 1.

3. An expression cassette, recombinant vector, transgenic cell line, recombinant bacterium or virus particle comprising the polynucleotide according to claim 2.

4. The expression cassette, recombinant vector, transgenic cell line, recombinant bacterium or virus particle according to claim 3, characterized in that, the virus particle is an adenovirus particle or a lentivirus particle.

5. An mRNA encoding the antigen according to claim 1.

6. A vaccine, which comprises the antigen according to claim 1, the polynucleotide according to claim 2, the expression cassette, recombinant vector, transgenic cell line, recombinant bacterium or virus particle according to claim 3 or 4, or the mRNA according to claim 5 as an active ingredient.

7. The vaccine according to claim 6, characterized in that, the vaccine includes one or more of inactivated vaccine, attenuated vaccine, DNA vaccine, mRNA vaccine, virus vector vaccine, subunit vaccine or virus particle; and / or, the vaccine further includes a pharmaceutically or veterinarily acceptable vehicle.

8. The vaccine according to claim 7, characterized in that, the vaccine further includes a pharmaceutically or veterinarily acceptable diluent, adjuvant or excipient.

9. The vaccine according to claim 7 or 8, characterized in that, the vaccine is an adenovirus vaccine.

10. A recombinant adenovirus vaccine, characterized in that, it includes chimpanzee adenovirus type 7, and the chimpanzee adenovirus type 7 is packaged with a recombinant vector; the recombinant vector includes: a backbone vector and a nucleic acid sequence containing a target gene connected to the backbone vector; the backbone vector is a replication-defective chimpanzee adenovirus type 7 vector; the target gene is: the polynucleotide according to claim 2 or the mRNA according to claim 5.

11. Use of the antigen according to claim 1, the polynucleotide according to claim 2, the expression cassette, recombinant vector, transgenic cell line, recombinant bacterium or virus particle according to claim 3 or 4, or the mRNA according to claim 5 in the preparation of a vaccine for preventing Zika virus or Dengue virus infection.

Citation Information

Patent Citations

  • Epitope-substituted vaccine for use in improving safety and immunogenicity against dengue viruses

    CN107405392A

  • Variant flavivirus envelope sequences and uses thereof

    CN109415414A