Nucleic acids encoding zika virus-like particles and their use in zika virus vaccines and diagnostic assays
Inventors
Chang, Gwong-Jen J. • Davis, Brent S.
Assignees
US Department of Health and Human Services
Publication Number
US-10947277-B2
Publication Date
2021-03-16
Expiration Date
2037-06-09
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Abstract
Transcriptional units encoding Zika virus (ZIKV) premembrane (prM) and envelope (E) proteins, which upon translation form Zika virus-like particles (VLPs), are described. Use of the transcriptional units and VLPs in three different ZIKV vaccine platforms is described. Immunoassay-based detection methods using ZIKV VLPs are described for the diagnosis of ZIKV infection.
Core Innovation
The invention discloses transcriptional units encoding Zika virus (ZIKV) premembrane (prM) and envelope (E) proteins. Upon translation, these proteins form Zika virus-like particles (VLPs). These transcriptional units and VLPs are utilized in various ZIKV vaccine platforms including plasmid DNA vaccines, recombinant adenovirus vectors, and recombinant adenovirus-vectored vaccines. Additionally, the invention provides methods for using the VLPs in immunoassay-based detection methods for diagnosing ZIKV infection.
The problem addressed arises from the public health threat posed by ZIKV, which has spread explosively and is linked to congenital birth abnormalities like microcephaly, as well as neurological disorders such as Guillain-Barré syndrome. The virus is challenging to diagnose due to its short viremic phase, and current control measures focus mainly on vector control. There is therefore a critical need for improved serodiagnostic assays and effective vaccines against ZIKV. The invention provides transcriptional units optimized for expression and VLP formation, alongside vaccine and diagnostic applications to address these needs.
Claims Coverage
The patent contains one independent claim focused on a ZIKV virus-like particle and several dependent claims relating to detection methods using this VLP.
Virus-like particle comprising modified ZIKV prM and E proteins
A virus-like particle (VLP) comprising Zika virus premembrane (prM) protein and envelope (E) protein, wherein the E protein includes specific amino acid substitutions: a glycine to lysine substitution at position 106 and a leucine to aspartic acid substitution at position 107, with numbering based on ZIKV strain MR766.
Method of detecting ZIKV-specific antibodies using modified VLPs
Methods of detecting Zika virus-specific antibodies in a biological sample by contacting the sample with the modified VLPs bearing the specified E protein mutations, forming VLP-antibody complexes, and detecting these complexes through means including the use of labeled antibodies or secondary antibodies.
Detection methods using immune complex formation on solid supports
Methods employing a secondary antibody or a ZIKV-specific antibody bound to a solid support to capture ZIKV-specific antibodies from biological samples, followed by exposure to the modified VLP to form immune complexes, and subsequent detection using labeled antibodies.
The patent claims focus primarily on a virus-like particle comprising ZIKV prM and mutation-modified E proteins that reduce cross-reactivity, alongside various immunoassay methods for detection of ZIKV-specific antibodies employing this VLP, providing both diagnostic and vaccine utility.
Stated Advantages
The invention provides a ZIKV vaccine capable of eliciting a strong and protective immune response in animal models with a single dose.
The modified virus-like particles with amino acid substitutions reduce flavivirus cross-reactive immune responses, enhancing vaccine safety.
The VLPs enable sensitive and specific immunoassay-based detection methods for diagnosing ZIKV infection.
Documented Applications
Use of ZIKV prM and E protein-encoding transcriptional units and the resulting VLPs in various vaccine platforms including plasmid DNA vaccines and recombinant adenovirus-vector vaccines to induce protective immunity against ZIKV.
Use of the VLPs in immunoassay detection methods such as antigen capture ELISAs, microsphere immunoassays, and indirect ELISA for sensitive and specific detection of ZIKV-specific antibodies in biological samples.
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