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Principal Investigator: Sumanth Gandra
Organization: WASHINGTON UNIVERSITY
Fiscal Year: 2024
Award: $201,208
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary/Abstract:
An antigen test for Neisseria gonorrhoeae (Ng) that is accurate, simple, scalable, non-invasive, rapid, and
effective at the point-of-care (POC), would transform public health decisions. Although antigen detection rapid
diagnostic tests (Ag-RDT's) for Ng are available, they have poor sensitivity (50% or less) compared to gold
standard nucleic acid amplification tests (NAAT). A NAAT based POC test was recently cleared by the US FDA,
however its use in resource-poor settings is limited by its high cost. To overcome these barriers for the first time,
we will harness ultrabright fluorescent nanoconstructs, called plasmonic-fluors, a recent breakthrough from our
labs that enables such antigen testing with sensitivity that matches NAATs. The objective of this proposal is to
develop an ultrasensitive plasmon-enhanced lateral flow assay (p-LFA) that detects the lipoprotein H.8 antigen
present on Ng surface. The rationale underlying this proposal is that a highly sensitive Ag-RDT that can match
the accuracy of NAAT could meet the critical need for diagnosing Ng infection at the POC and in resource-limited
settings. We will achieve this by pursuing two specific aims: 1) Develop and optimize the p-LFA for detecting
Ng lipoprotein H.8 antigen in urine samples obtained from healthy people. 2) Determine the diagnostic accuracy
of the Ng antigen test compared to gold standard NAAT in urine specimens from patients with suspected Ng
infection. The proposed approach is innovative in that it harnesses plasmonic-fluor as a fluorescent nanolabel in
a LFA as opposed to the conventional gold nanoparticles, which provide only a weak colorimetric signal. With
over 1000-fold improvement in sensitivity, this approach has the potential to transform antigen testing. The
proposed research is significant as the novel p-LFA will meet the critical needs for widespread Ng testing
scalability, speed, and low cost. The expected outcome of this work is a simple, non-invasive, Ag- RDT for Ng
infection, implemented as a LFA that can replace NAAT by virtue of its accuracy and low cost in resource-limited
settings. This test will have a tremendous positive impact immediately as it will be applicable to large scale Ng
testing with an inexpensive test strip and minimal battery-powered portable equipment, without relying on skilled
personnel. Furthermore, this test will serve as a prototype for ultrasensitive antigen tests applicable to many
other infectious diseases in addition to the possibility of incorporating multiple antigens on a LFA for diagnosing
other sexually transmitted infections such as chlamydia and trichomoniasis in addition to Ng.
Terms: <Accounting><Accuracy of Diagnosis><Address><Antigen Presentation><Antigens><Antimicrobial Resistance><Assay><Bioassay><Biological Assay><COVID detection><COVID-19 antigen><COVID-19 detection><COVID19 detection><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Centers for Disease Control><Centers for Disease Control and Prevention><Centers for Disease Control and Prevention (U.S.)><Characteristics><Chlamydia><Clinical><Clinical Sensitivity><Communicable Diseases><Development><Devices><Diagnosis><Diagnostic><Diagnostic tests><ELISA><Enzyme-Linked Immunosorbent Assay><Equipment><Feasibility Studies><Flour><Fluorescence><Future><Generations><Goals><Gonococcal Infection><Gonococcus><Gonorrhea><Health><Hospitals><Human Resources><Incidence><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Intracellular Communication and Signaling><Investigation><Jewish><Judaism><LMIC><Label><Laboratories><Life><Lipoproteins><Low-resource area><Low-resource community><Low-resource environment><Low-resource region><Low-resource setting><Manpower><Methods><Microbiology><Miyagawanella><Molecular><N gonorrhea><N gonorrhoeae><N. gonorrhea><N. gonorrhoeae><Nature><Neisseria gonorrhea><Neisseria gonorrhoeae><Nucleic Acid Amplification Tests><Nucleic Acid Testing><Nucleocapsid Proteins><Outcome><Patients><Persons><Process><Public Health><Rapid diagnostics><Reader><Reporting><Reproducibility><Research><Research Resources><Research Specimen><Resolution><Resource-constrained area><Resource-constrained community><Resource-constrained environment><Resource-constrained region><Resource-constrained setting><Resource-limited area><Resource-limited community><Resource-limited environment><Resource-limited region><Resource-limited setting><Resource-poor area><Resource-poor community><Resource-poor environment><Resource-poor region><Resource-poor setting><Resources><Running><SARS-CoV-2 antigen><SARS-CoV-2 detection><Sampling><Sensitivity and Specificity><Sexually Transmitted Diseases><Sexually Transmitted Disorder><Sexually Transmitted Infection><Signal Transduction><Signal Transduction Systems><Signaling><Specificity><Specimen><Speed><Surface><Technology><Testing><Time><Trichomonas Infections><Trichomonosis><United States><United States Centers for Disease Control><United States Centers for Disease Control and Prevention><Urine><Validation><Venereal Diseases><Venereal Disorders><Venereal Infections><Work><anti-microbial resistant><antigen based detection><antigen based test><antigen detection><antigen test><bedsonia><biological signal transduction><coronavirus detection><coronavirus disease 2019 antigen><coronavirus disease 2019 detection><coronavirus disease detection><cost><depository><detect COVID><detect COVID-19><detect COVID19><detect SARS-CoV-2><detect antigen><detect coronavirus><detect coronavirus disease><detect severe acute respiratory syndrome coronavirus 2><detection assay><detection limit><detection test><detection tests><developmental><diagnostic accuracy><diagnostic technologies><enzyme linked immunoassay><fluorophore><follower of religion Jewish><gold nano particle><gold nanoparticle><healthy volunteer><immunogen><improved><infection rate><innovate><innovation><innovative><instrumentation><lateral flow assay><lateral flow test><low and middle-income countries><nano><nano gold><nano label><nanoGold><nanolabel><novel><personnel><plasmonics><point of care><point of care testing><portability><prototype><rate of infection><repository><resistance to anti-microbial><resistant to antimicrobial><resolutions><screening><screenings><severe acute respiratory syndrome coronavirus 2 antigen><severe acute respiratory syndrome coronavirus 2 detection><sexually acquired infection><skills><test strip><tool><trichomoniasis><validations>