Immunoassay methods and compositions for detecting infection involving use of test antigens as cross-reactive control antigens
Inventors
Needham, James William • Raychaudhuri, Syamal
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Publication Number
US-10955414-B2
Publication Date
2021-03-23
Expiration Date
Abstract
The present invention relates to compositions and methods involving diagnostic tests with multiple test antigens. The present invention involves the expanded use of test antigens as cross-reactive control antigens (CCAs). The invention advantageously provides for enhanced test results analysis by simultaneously providing both test antigen and CCA signal results. These results, in turn, allow useful sample comparison and cross-reference between samples to more accurately identify and verify the fidelity of test results obtained for multiple infective agents at once. The present invention may include compositions and methods for detecting infection by Zika virus or another flavivirus, and may distinguish between infections caused by genetically similar agents.
Core Innovation
The invention provides immunoassay systems and diagnostic assay formats for distinguishing infections with genetically similar viruses by expanding the use of cross-reactive control antigens (CCAs). It addresses immunological challenge created by cross-reactivity among closely related viruses, including flaviviruses such as Zika, dengue, and West Nile, and alphaviruses such as chikungunya. The approach uses multiple antigens per sample to generate parallel signals that can be compared to reduce false positives arising from cross-reactive binding.
In the assay formats, common bound components and common test antigen conjugates are used together with two or more different test antigens derived from different species within a shared viral genus, selected from the flavivirus genus and the alphavirus genus. At least one different test antigen is a cross-reactive control antigen, and the assay uses ratio-based interpretation in which the ratio of binding of each different test antigen to the common bound component indicates the likelihood of cross-reactivity error. The document further frames target/CCA/NCA relationships and uses immune status ratios (ISR) and related antigen/CCA/NCA ratios to guide categorization.
The interpretation logic includes defining target and control relationships and applying immune status ratio (ISR) calculation and cutoffs to categorize results, including Zika interpretation. The described workflow uses antigen panels with virus-like particles (VLPs) and provides validation data, including clinical and field studies, that report specificity and cross-reactivity performance metrics and interference testing. Example antigen panels are used to demonstrate categorization accuracy under cross-reactive conditions for related infective agents.
Claims Coverage
The independent claims comprise three inventive features centered on multi-antigen immunoassay/detection architectures that incorporate cross-reactive control antigens and interpret binding using ratio and immune status ratio concepts to distinguish related infective agents within shared viral genera (flavivirus or alphavirus).
Common components with multiple different test antigens from a shared viral genus
A diagnostic assay comprising a common bound component, a common test antigen conjugate, and two or more different test antigens, wherein each test antigen binds to each of the common bound component and the common test antigen conjugate, and each different test antigen indicates the presence or absence of a particular bound component; the different test antigens are derived from different species within a shared viral genus selected from the flavivirus genus and the alphavirus genus.
Cross-reactive control antigen use with ratio indicating likelihood of cross-reactivity error
At least one of the different test antigens is a cross-reactive control antigen, and the ratio of binding of each of the different test antigens to the common bound component indicates the likelihood of cross-reactivity error.
Detectable signal generation using test antigens as cross-reactive control antigens for in vitro distinguishing
A method for distinguishing between related infective agents in vitro, comprising generating a detectable signal from at least one of at least two different test antigens, and using each of the at least two different test antigens as a cross-reactive control antigen, wherein each test antigen binds to each of a common bound component and a common test antigen conjugate, each of the different test antigens indicates the presence or absence of a particular bound component, and the different test antigens are derived from different species within a shared viral genus selected from the flavivirus genus and the alphavirus genus.
Overall claim coverage centers on multi-antigen immunoassay and detection architectures that incorporate cross-reactive control antigens and interpret binding using ratio and immune status ratio concepts to distinguish related infective agents within shared viral genera.
Stated Advantages
Reduces false positives from cross-reactivity by comparing parallel signals generated from multiple antigens per sample.
Indicates the likelihood of cross-reactivity error using binding ratios to support discrimination among genetically similar viruses.
Documented Applications
Distinguishing infections with genetically similar viruses, including flaviviruses (Zika, dengue, West Nile) and alphaviruses (chikungunya), using immunoassay systems and diagnostic assay formats based on cross-reactive control antigens and ratio-based interpretation.
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