Specific Rapid Antigen Diagnostic Tests Based on Cross-Reactive Monoclonal Antibodies

Applications

This technology has applications in diagnostic development for emergent infectious diseases.

Problem Addressed

New infectious diseases arise regularly and present urgent public health threats, as in the recent cases of Zika virus and Ebola virus. Containing these new infectious diseases is a major public health challenge, and point-of-care (POC) diagnostics are a critical tool to aid patient care, resource allocation, and disease containment. However, developing new antibodies for these POC diagnostics can take 16-24 months, which is far too late for newly arising infectious disease crises. Additionally, developing a new antibody diagnostic can cost hundreds of millions of dollars. There is therefore a dire need for strategies that accelerate the development of POC diagnostics. This technology is a novel method for rapidly developing diagnostics from existing antibodies.

Technology

This technology leverages cross-reactive antibodies to rapidly develop diagnostics for newly arising infectious diseases. New infectious diseases share sequence similarity with other closely related diseases; for example, Zika is part of the flaviviridae family, which also includes Dengue virus. The inventors exploited the similarities between Zika and Dengue viruses to develop Zika diagnostics by identifying Dengue antibodies that cross-react with Zika. The technology uses a paper-based lateral flow assay and red or blue colorimetric nanoparticles conjugated to Dengue or Dengue + Zika reactive antibodies to determine if a patient has Zika and/or Dengue. The antibody-conjugated nanoparticles are mixed with a patient sample, where they bind any present Zika or Dengue antigen. Next, the sample is loaded into the paper assay where a second set of antibodies traps the antigen-bound nanoparticles in discrete lines. The assay is then read-out visually by identifying the colors associated with each location along the paper strip, much like a pregnancy test. Importantly, this technology is able to distinguish between Zika infection and Dengue infection, which is particularly important since these diseases can co-localize in a geographic region. The inventors used a similar strategy to develop Ebola diagnostics from Marburg virus antibodies, which suggests that this technique could be a generalizable strategy to rapidly generating diagnostics for emergent infectious diseases.

Advantages

  • Paper-based lateral flow assays for Zika and Ebola developed from existing cross-reactive antibodies
  • Capable of distinguishing between emergent disease and related family member (ex. Zika and Dengue or Ebola and Marburg virus) through the use of colorimetric nanoparticles
  • Generalizable strategy to rapidly generate diagnostics for emerging infectious diseases