Document text
Principal Investigator: Amanda Burnham-Marusich
Organization: DXDISCOVERY, INC.
Fiscal Year: 2024
Award: $999,716
Funding agency: National Institute of Allergy and Infectious Diseases
Pertussis (Whooping cough) is a highly contagious, airborne disease that is rapidly re-emerging as a serious
public health threat in the United States. Despite high vaccine coverage, annual reported cases in the U.S. have
been increasing recently, with an average of 25,000 per year from 2010-2019. This is a level unseen since the
early 1960s. Diagnosis of pertussis is challenging because its early symptoms (during the contagious catarrhal
stage, prior to paroxysmal cough) overlap with other respiratory diseases. This is analogous to the diagnostic
challenge of COVID-19. The ongoing COVID-19 pandemic has illustrated the critical public health importance of
accessible, rapid diagnostics for controlling the spread of highly transmissible respiratory diseases, a category
that includes pertussis. Consequently, as with COVID-19, there is a critical need to develop improved pertussis
diagnostics to enable prompt, appropriate patient treatment as well as limit needless community transmission.
The project goal is a rapid, point-of-care (POC), lateral flow immunoassay (LFIA) to detect Bordetella pertussis
antigen from nasopharyngeal specimens. The target population will be symptomatic patients who present in
pediatrician offices, urgent care clinics, or small hospital ERs. The product will be a sensitive and specific test
that enables immediate action, akin to other highly used and accepted LFIAs (e.g. COVID-19, RSV).
This proposal builds on data and results from Phases I and II. First, the B. pertussis protein tracheal colonization
factor A (TcfA) was identified as a specific biomarker for presence of the bacterium. Second, a library of epitope-
mapped monoclonal antibodies (mAbs) with high affinity and specificity to TcfA was developed. Third, over 784
permutations of mAb combinations were evaluated for construction of a LFIA. Fourth, the prototype LFIA’s
configuration was optimized for high specificity and sensitivity for detection of both purified TcfA and clinically
relevant concentrations of B. pertussis cells. Fifth, the prototype LFIA showed high sensitivity and specificity for
diagnosis of pertussis in a baboon model. Finally, proof-of-concept was demonstrated with patient specimens.
Per the original plan, Phase IIb builds on Phases I and II to deliver an FDA-cleared diagnostic. Three aims are
proposed. Aim 1 includes an FDA Pre-Submission and transitions from a research-grade, prototype LFIA to a
commercial-grade product made under GMP. Aim 2 is a pre-clinical evaluation of precision and reproducibility,
limit of detection, analytical specificity and inclusivity, stability, ruggedness, interfering substances, and microbial
interference. Aim 3 is a clinical evaluation that will end with a FDA 510(k) Submission. If successful, this study
will deliver a pertussis POC test that is easily accessible to all clinics and that provides results in an actionable
timeframe – thereby reducing patient morbidity and preventing unnecessary community transmission.
Terms: <Affinity><Agreement><Annual Reports><Antibodies><Antigen Targeting><Antigens><B pertussis><B pertussis infection><B. pertussis><B. pertussis infection><Baboons><Bacteria><Blood group antigen S><Bordetella pertussis><Bordetella pertussis infection><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 antigen><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><CV-19><Case Study><Categories><Cell Body><Cell surface><Cells><Clinic><Clinical><Clinical Evaluation><Clinical Testing><Clinical Treatment Moab><Co(beta)-cyano-7''-(2-methyl)adeninylcobamide><Commercial grade><Communities><Coronavirus Infectious Disease 2019><Coughing><Country><Data><Detection><Diagnosis><Diagnostic><Disease><Disease Outbreaks><Disorder><Early Diagnosis><Early treatment><Electricity><Epitope Mapping><Equipment><Goals><H Pertussis><H. Pertussis><Haemophilus pertussis><Healthcare><Hospitals><Hour><Immunoassay><Infant><Infection><Laboratories><Lateral><Libraries><Linear Sequence Epitopes><Measures><Modeling><Monoclonal Antibodies><Morbidity><Morbidity - disease rate><Nasopharynx><Nucleic Acids><Outbreaks><Papio><Papios><Patients><Performance><Pertussis><Phase><Preparation><Proteins><Protocol><Protocols documentation><Public Health><Rapid diagnostics><Reaction><Reproducibility><Research><Research Resources><Research Specimen><Resources><Respiratory Disease><Respiratory System Disease><Respiratory System Disorder><Rhinopharynx><S antigen><SARS-CoV-2 antigen><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Sampling><Savanna Baboons><Sensitivity and Specificity><Serology><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severity of illness><Specificity><Specimen><Speed><Statistical Data Analyses><Statistical Data Analysis><Statistical Data Interpretation><Symptoms><Target Populations><Testing><Trachea><Trachea Proper><Transmission><United States><Vaccines><Visual><Whooping Cough><antigen based detection><antigen based test><antigen detection><antigen test><case report><child health care provider><child healthcare provider><clinical relevance><clinical test><clinically relevant><community spread><community transmission><community-level spread><community-level transmission><coronavirus disease 2019><coronavirus disease 2019 antigen><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus infectious disease-19><cross reactivity><design><designing><detect antigen><detection limit><detection sensitivity><disease duration><disease length><disease severity><early detection><early therapy><economic impact><factor A><fungus><health care><illness length><immunogen><improved><infected with B pertussis><infected with B. pertussis><infected with Burkholderia pertussis><mAbs><microbial><monoclonal Abs><nasopharnygeal><nasopharyngeal swab><pediatric care provider><pediatric health care provider><pediatric healthcare provider><pediatric provider><pediatrician><point of care><point of care testing><pre-clinical><pre-clinical evaluation><preclinical><preclinical evaluation><preparations><prevent><preventing><prospective><prototype><rapid assay><rapid test><rapid tests><research clinical testing><severe acute respiratory syndrome coronavirus 2 antigen><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><specific biomarkers><statistical analysis><tool><transmission process><urgent care><waiver><windpipe>