Virus-like particles comprising zika antigen
Inventors
Assignees
American Type Culture Collection ATCC
Publication Number
US-11179460-B2
Publication Date
2021-11-23
Expiration Date
2038-06-22
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Abstract
The invention is related to chimeric Virus-Like Particles (VLPs) containing and displaying epitopes and antigen from Zika Virus (ZIKV); and to methods for creation and production of such chimeric VLPs to their applications, including but not limited to vaccines, diagnostics, clinical studies, assay development and antibody discovery.
Core Innovation
The invention provides chimeric Virus-Like Particles (VLPs) that contain and display Zika virus (ZIKV) antigens and epitopes, and materials, methods, and compositions for their production and use. These VLPs are engineered by fusing immunogenic regions from ZIKV proteins, such as Envelope protein Domain III (EDIII), NS1, prM/M, or Capsid (C), with a heterologous core protein scaffold derived from Woodchuck Hepatitis core Antigen (WHcAg). The Zika-derived peptides are inserted into specific sites within the WHcAg protein so the resulting chimeric peptides assemble into multimeric VLPs capable of presenting Zika epitopes in immunogenic conformations.
The problem addressed is the lack of an effective, safe, and scalable vaccine or therapeutic for Zika virus infection. Current ZIKV vaccines such as live attenuated and inactivated virus have safety concerns, difficulty achieving proper epitope presentation, and are costly to manufacture. There is also a need for improved diagnostics due to the similarity of Zika symptoms to other arboviruses and the existence of cross-reactive antibodies with related flaviviruses, which complicates both accurate diagnosis and vaccine design.
This invention utilizes the structural vaccinology approach to select Zika epitopes with high specificity and immunogenicity for insertion into the WHcAg scaffold, creating VLPs that mimic the native viral structure and display antigens in a repetitive and stable array. The technology enables large-scale, cost-effective production—especially in yeast expression systems—and the resulting VLPs are suitable for use as vaccines, diagnostics, antibody detection, and assay development. The VLP platform offers improved safety for high-risk populations, potential cross-strain protection, and facilitates robust antibody and cell-mediated immune responses.
Claims Coverage
The patent contains seven primary inventive features defined in the independent claims, covering chimeric peptides/vectors, VLPs, compositions, kits, vaccines, and detection methods.
Chimeric peptide comprising ZIKV antigen and WHcAg sequence
A chimeric peptide consisting of: - A first peptide selected from SEQ ID NOS: 2-11, 22-33, 46, 47, 50, and 51 (representing specific ZIKV antigens). - Operably linked to a second heterologous peptide with an amino acid sequence at least 80% identical to the Woodchuck Hepatitis core Antigen protein (WHcAg, SEQ ID NO: 1) or a functional fragment thereof. The WHcAg portion serves as a scaffold for repetitive Zika antigen display.
Polynucleotide encoding the chimeric peptide
A polynucleotide comprising a nucleotide sequence encoding the chimeric peptide detailed above, enabling the expression of the ZIKV-antigen-displaying chimeric peptide.
Expression vector containing the polynucleotide
An expression vector comprising the polynucleotide that encodes the chimeric peptide, operably linked to an expression control sequence. This enables recombinant expression of the chimeric peptide in suitable host cells.
Recombinant host cell with expression vector
A recombinant host cell comprising the aforementioned expression vector. The host cell is selected from eukaryotic cells (mammalian, yeast, insect, plant, amphibian, avian) or prokaryotic cells.
Virus-like particle (VLP) comprising the chimeric peptide
A virus-like particle comprising the chimeric peptide as described above. The claim further includes VLPs attached to solid supports such as microbeads, assay plates, test strips, or filters.
Antigenic composition comprising the VLP
An antigenic composition comprising the VLP described above, at a concentration of about 0.1–2000 μg/ml in a pharmaceutically acceptable carrier, diluent, stabilizer, preservative, or adjuvant, wherein the composition induces a protective immune response and/or anti-Zika neutralizing or protective antibodies.
Detection or measuring antibodies to Zika virus using VLPs
A method comprising: 1. Contacting the VLP with a biological sample under conditions suitable for antigen-antibody complex formation. 2. Measuring or detecting antibodies to Zika virus by detecting/measuring an antigen-antibody complex formed between antibodies in the biological sample and the VLP.
The inventive features establish a platform for creating virus-like particles that present Zika antigens using a hepadnavirus core scaffold, methods and vectors for producing them, formulations for immunogenic compositions and kits, and means for utilizing these VLPs in diagnostics and immune response generation.
Stated Advantages
VLPs provide high safety due to the absence of replicating viral genetic material.
The invention enables cost-effective and scalable large-scale manufacture using systems such as yeast.
VLPs maintain the ZIKV epitope architecture and offer potential cross-protection across multiple ZIKV strains.
The platform is particularly amenable to defined quality control strategies for large scale production.
Compared to live attenuated and inactivated virus vaccines, the VLP strategy possesses a higher safety profile, especially for immunocompromised individuals and pregnant women.
VLPs express the immunological entity at high concentration, in appropriate conformation, and with greater stability compared to purified protein vaccines.
The VLP-based vaccine can stimulate both robust B-cell and T-cell immune responses, including neutralizing and protective antibodies.
The VLP platform is also compatible with varied adjuvant formulations for further optimization of immunogenicity.
Documented Applications
Use as vaccines to induce protective immune responses against Zika virus, including in high risk populations.
Use in diagnostics, such as in ELISA and Lateral Flow Immunoassay (LFIA), for detecting or measuring anti-Zika antibodies or Zika virus infection in biological samples.
Use in screening and discovery of anti-Zika antibodies.
Use in assay development for the quantification or detection of Zika immune responses post-infection or immunization.
Use in clinical studies to evaluate vaccine safety, immunogenicity, or protection in animal models, including protection against fetal transmission.
Use in kits and articles of manufacture for immunoassays, including test strips, assay plates, and microbeads containing the VLP.
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