Antibody-based assays or immunodiagnostics are important tools during clinical vaccine testing, disease outbreaks, or a biological weapon incident. In disease outbreaks, diagnostics are the first line of defense in the identification of the causative agent, treatment decisions, and eventually control and prevention of future outbreaks.
Most assays rely on complex biological materials such as viral extracts or recombinant proteins for testing antigen-antibody interactions. However, the use of complex biological materials are typically costly, inconvenient to prepare, and pose a biohazard for diagnostics developers, researchers, and end-users.
Virus-like particles (VLPs) have emerged as a promising advancement over conventional viral extracts or recombinants used in assays. By combining a VLP with a bead-based immunoassay format, it is possible to obtain a sensitive and sustainable multiplexed assay for detection of antibody responses to assorted glycoprotein antigens. Army researchers are leveraging this knowledge into sustainable VLP-based reagents that are safe and readily available for infectious diseases and biodefense applications.
Army researchers have developed a novel sustainable biosafety level 2 (BSL-2) diagnostic reagent based on VLPs conjugated to microspheres. As a proof of concept, Venezuelan equine encephalitis virus (VEEV) E1/E2 glycoproteins were expressed on a retroviral core VLP and conjugated to fluorescent, magnetic microspheres to create VLP conjugated microspheres (VCMs). When incorporated onto the MAGPIX platform, the VCMs were shown to detect both IgG and IgM in nonhuman primates and human clinical samples with enhanced sensitivity over traditional ELISA formats in both a singleplex and multiplex format.
This VCM approach was further used to develop the eastern equine encephalitis virus (EEEV), western equine encephalitis virus (WEEV), and chikungunya virus (CHIKV) assays, which when used in various multiplexed formats, provided differential diagnosis between Old-World and New-World alphaviruses, tracking of IgM response to VEEV and WEEV challenge in NHPs, and measurement of IgG response to V/E/WEEV vaccination in human serum samples. Taken together, these results demonstrate that VCMs can offer a sustainable and flexible approach for developing immunodiagnostics for use in multiple applications, including animal modeling, serosurveillance, and improved point of care diagnostics.
- Enables differential diagnosis of infections caused by different viruses having similar clinical symptoms
- Preliminary testing demonstrates stability in extended storage without the need for a cold chain facility
- Can be used to monitor pathogen exposure over time
- Faster sample to answer time relative to traditional ELISA methods
- Flexible, innovative immunoassay system improves sensitivity by up to 2-logs
- US patent serial number 62/581,023 available for license
- Potential for collaboration with Army researchers
- Proof-of-concept testing performed