DXDISCOVERY INC — Department of Health and Human Services SBIR Phase II: R

Description

Project Summary Pertussis is rapidly re emerging as a serious public health threat in the United StatesDespite high vaccine coverage nationallyannual reported cases in the U Shave been increasing recentlywith ayear high ofinMoreoverreported cases represent a large underestimate of pertussis infectionsDiagnosis of early pertussiscatarrhal stageprior to paroxysmal coughis particularly challenging because its symptoms are non specific and because there are no assays that can diagnose pertussis at the point of patient careThere is a critical need to develop improved pertussis diagnostics to fill this gap because pertussis treatment reduces disease severity and durationbut only if treatment begins prior to paroxysmal coughThe goal of this project is to develop a rapidandltminpoint of carePOCimmunoassay to detect Bordetella pertussis during early diseaseThe target population will be infants with the non specificrespiratory tract infection symptoms of early stage pertussisThe approach will be detection of Bpertussis antigens from nasopharyngealNPsamples by lateral flow immunoassayLFIThe POC diagnostic that we propose is innovative because it will change the current clinical status quoa pertussis LFI will give healthcare providers immediate access to actionable and relevant informationwhich will enable rapid and appropriate patient careIn Phase Iwe demonstrated the feasibility of our LFI approach and achieved every milestone of our Phase I Specific AimsSpecificallywe used an innovative bioinformatics based strategy to develop epitope specific polyclonal antibodiespAbsagainst a Bpertussis antigen that has both cell associated and secreted isoformsWe then validated our pAbs for reactivity with both isoforms in sensitive and specific LFI prototypesThe limit of detection of our current pAb based LFI isxCFUwhich is well below the typical bacterial burden of infant NP washestoCFU mlor swabsCFUIn Phase IIwe will build on our Phase I results and develop an advanced monoclonal antibodymAbbased LFI commercial diagnosticWe will focus on developing mAbs against the validated biomarker epitopesAimand incorporating these mAbs into an LFI with sensitivity and commercialization potential superior to that of the Phase I pAb based prototypesWe will ioptimize the mAb based LFI for analytical sensitivity in NP samplesAimiidetermine clinical sensitivity and specificity at different disease stages in a clinically relevantbaboon infection modelAimand iiidetermine the LFIandapos s limit of detection with patient samplesAimTogetherthis data will guide our FDAkPre Submission at the end of Phase IISuccessful completion of our milestones will ultimately yield a rapidaffordablePOC immunoassay that will dramatically increase early pertussis diagnosiswhich will iinitiate prompt treatmentiireduce disease severity and durationiiilimit outbreaks by preventing unnecessary transmissionand ivsave infant lives Project Narrative Pertussiswhooping coughis rapidly re emerging as a serious public health threat in the United StatesThe goal of this project is to resolve a critical public health need for improved pertussis diagnosticsby developing a point of carePOCimmunoassay that can diagnose early stage pertussis in minutesat very low costand without the need for specialized equipment or user expertiseA POC immunoassay will dramatically increase early pertussis diagnosiswhich will iinitiate prompt treatmentiireduce disease severity and durationiiilimit outbreaks by preventing unnecessary transmissionand ivsave infant lives