DXDISCOVERY INC — Department of Health and Human Services SBIR Phase I: NIAID

Description

DESCRIPTION provided by applicant Pertussis is a serious and potentially life threatening respiratory disease caused by the bacterium Bordetella pertussis Worldwide million people become ill with pertussis each year and of these patients die Despite high vaccine coverage in the United States there were still over pertussis cases reported in the U S in Rapid diagnosis of pertussis is critical because treatment and outbreak containment are only effective if initiated early in the disease Currently there are no assays that can rapidly and accurately detect early stage pertussis The goal is to develop a rapid point of care POC immunoassay to detect B pertussis during early disease The target population will be infants who present with the non specific respiratory tract infection symptoms of early pertussis prior to onset of paroxysmal cough The approach will be detection of B pertussis antigens from nasopharyngeal swabs by lateral flow immunoassay LFI The product will be an assay relevant to i U S pediatrician offices and ii international clinics in low resource settings a sensitive and specific test that delivers results in min at very low cost without specialized equipment or user expertise In preliminary studies we used a bioinformatics analysis to identify five high priority B pertussis protein antigens for further stdy Specific Aim will develop epitope specific polyclonal antibodies pAbs for detection of B pertussis antigens pAbs will be screened to select those that i react with B pertussis proteins ii react with B pertussis but not other bacteria found in the nasopharynx iii can function in pairs to bind the antigen in the sandwich format necessary for LFI construction and iv detect antigen in patient nasopharyngeal samples Only pAbs that meet all the criteria will be advanced to LFI prototype development in Specific Aim Specific Aim will determine the limit of detection of B pertussis by LFI by optimizing the physical and biological components of the LFI prototypes Based on previously determined B pertussis loads in infant NP swabs of bacteria per swab the benchmark for sensitivity is detection of CFU per swab Together the experiments of Phase I will determine which B pertussis antigen epitopes can produce pAb pairs that yield LFI prototypes with the required sensitivity A Phase II study would develop monoclonal antibodies mAbs against the validated epitopes incorporate them into an LFI and perform detailed pre clinical studies Successful navigation of a full clinical trial in Phase III would ultimately yield a POC immunoassay that could dramatically increase early pertussis diagnosis limit pertussis transmission during community outbreaks and save patient lives PUBLIC HEALTH RELEVANCE Although vaccine preventable pertussis remains a serious disease in both developed and resource limited nations causing million illnesses and deaths annually The goal of this project is to develop a point of care POC immunoassay that can diagnose early stage pertussis within minutes at a very low cost and without the need for specialized equipment or a high level of user expertise A POC immunoassay will save lives and improve public health through early diagnosis effective treatment and outbreak containment