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Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 3.67M | Year: 2012

This project is aimed at the development of an enzyme immunoassay (ELISA) for screening blood for antibodies to Babesia microti. Human babesiosis is a malaria-like illness due to infection of red blood cells by various species of protozoan parasites belonging to the genus Babesia. Most human infections reported in the United States are caused by B. microti which is endemic in parts of the northeast and north central United States. B. microti infections are often asymptomatic but can also progress to severeillness and even death, particularly in individuals who are immunosuppressed, asplenic or elderly. Recent cases of fatal transfusion-transmitted babesiosis have led to the identification of this pathogen as a significant threat to the blood supply. Currently no commercial, validated and FDA approved test are available for B. microti, and donor questionnaires have proven ineffective in preventing introduction of Babesia into the blood supply. Tests now in use including immunofluorescence, microscopy and PCRare not easily adaptable to high throughput blood screening. This proposal describes the development and clinical trial of a microplate-based Babesia ELISA which can be performed on an automated, high throughput platform, with the sensitivity and specificity required for blood screening. The research plan has five specific aims: 1) completion of assay development, proceeding from an optimized RandD prototype to a manufacturable kit, 2) manufacturing scale up, 3) evaluation of assay performance on blood donors from Babesia endemic and non-endemic areas in an IND clinical trial, 4) follow-up study of seropositive donors to inform donor deferral and re-entry policy, and 5) preparation and submission of a BLA application to the FDA for licensure for blood screening use.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 3.61M | Year: 2015

DESCRIPTION provided by applicant In this Phase II project development and clinical validation of an ELISA test for in vitro diagnosis of Babesia microti infection will be completed Babesiosis is an emerging tick borne parasitic disease which may cause severe to fatal illness in immunocompromised or otherwise weakened patients and may be carried in the blood subclinically in up to of the population in endemic areas Recent cases of fatal transfusion transmitted babesiosis have also led to the identification of this pathogen as a significant threat to the blood supply However currently no commercial validated and FDA approved tests are available for B microti Babesiosis is currently diagnosed by immunofluorescence staining microscopy of blood smears and or PCR None of these procedures are easily adaptable to routine clinical laboratory use In Phase I we developed a microplate based ELISA using a mixture of novel synthetic B microti peptide antigens comprising immunodominant epitopes that were demonstrated to be diagnostically significant markers of infection The five peptide sequences were identified through screening of libraries of overlapping peptides derived from members of the BMN family of B microti proteins a group previously identified as highly immunoreactive against babesiosis patient sera Several of these peptides and epitopes have not previously been recognized as immunodominant and represent new discoveries Sensitivity of among confirmed babesiosis cases was achieved along with specificity above in low risk blood donors and other controls The peptides have been combined in a single well ELISA format using an innovative immobilization chemistry The prototype ELISA will be optimized with respect to peptide stoichiometry and all other assay parameters and scaled up for manufacturing in Phase II To validate assay performance a clinical study will be carried out in Phase II in which the B microti ELISA will be compared with PCR and blood smear which are considered gold standard assays for Babesia infection A retrospective clinical study will evaluate assay performance on well characterized samples from confirmed babesiosis cases while a prospective study will examine undiagnosed patients seen at tick borne disease clinics at three medical centers in regions of the Northeast and Midwest that are highly endemic for B microti The clinical study will determine the performance of the B microti ELISA vs PCR blood smear and immunofluorescence for diagnosis of B microti infection Results will be submitted in a k application to FDA for clearance of the B microti ELISA for in vitro diagnostic use PUBLIC HEALTH RELEVANCE Babesiosis is an emerging tick borne parasitic infection which can produce severe to fatal illness especially in immunocompromised or weakened patients However no FDA approved tests are currently available to aid in clinical diagnosis of this disease This project will lead to the development validation FDA approval and commercial availability of the first simple accurate and user friendly diagnostic test for babesiosis


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 1.99M | Year: 2015

DESCRIPTION provided by applicant The incidence of invasive fungal infections and in particular Candida infections the fourth most common nosocomial pathogen has continued to increase over the past years This increase is due to the increasing numbers of patients subjected to severe immunosuppression as a result of transplant procedures chemotherapy regimens advances in medical and surgical therapies and the increased use of invasive devices such as intravascular central lines While the majority of invasive fungal disease IFD is caused by species of Candida and Aspergillus other rare fungal pathogens such as Cryptococcus Coccidioides and Zygomycetes have become more prevalent in recent decades and are associated with exceedingly high mortalities Candidiasis Aspergillosis Zygomycetes Cryptococcus Coccidioidomycosis and Blastomycosis Due to the slow turnaround time of current diagnostic methods proper treatment of IFD is often delayed contributing to the high mortality rates associated with this disease Microbiologic culture the current diagnostic standard requires on average hours for completion and fails to detect roughly of fungal species As proper treatment of IFD calls for prompt and accurate diagnosis an unmet need in the area of fungal diagnostics is a platform that can provide early detection sensitive results species level discrimination and multiplex capability Several molecular approaches have been developed to address this need but have failed to meet all these requirements Immuneticsandapos fungal microarray assay IFM assay uses PCR followed by hybridization on a microarray with species specific probes offering a solution to this unmet need by providing a sensitive and rapid hour test for a range of fungal pathogens in a multiplex format using whole blood samples rather than blood cultures In this Phase II application we propose further development and clinical validation of the IFM assay for the detection and diagnosis of infection with invasive fungal species The clinical study will be carried out in collaboration with two medical institutions specializing in care and treatment of fungal infections and will comprise prospective and retrospective evaluations on clinical blood samples obtained from patients at high risk for or with known fungal infections Regulatory approval from FDA for in vitro diagnostic use of the IFM assay will be sought upon successful completion of the clinical study upon which the IFM kit will be commercialized as a standalone molecular diagnostic assay This product offers a rapid sensitive and multiplexed approach that meets the requirements of an ideal diagnostic platform for IFD By significantly reducing time to detection this innovative platform will lead to changes in the treatment of IFD most notably faster treatment with a targeted anti fungal PUBLIC HEALTH RELEVANCE The incidence of fungal infections most of which are associated with high mortality has continued to increase over the past years Current fungal diagnostic methods are limited by number of pathogens detected turnaround time and low sensitivity We propose development and clinical validation of a rapid multiplexed microarray based molecular test that will significantly improve the detection and treatment of invasive fungal disease


Patent
Immunetics, Inc. | Date: 2015-03-23

Assay devices, assay detection systems, and methods comprising same for analytical tests, medical assays, diagnostic tests, medical diagnosis, risk assessment, or quality control purposes are provided. These devices, systems, and methods are designed to be employed at the point of care, such as in emergency rooms, operating rooms, hospital laboratories and other clinical laboratories, doctors offices, in the field, or in any situation in which a rapid and accurate result is desired. The systems and methods process samples, such as clinical, biological, or blood sample, and read data from colorimetric based biochemical assays to provide an indication of the presence or absence of a bacterial, fungal, or viral contaminants therein. The assay devices include an optical reader apparatus and barcode scanner for reading and matching the test results to identification information provided by the barcodes to facilitate ease of tracking compliant and noncompliant samples.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 600.00K | Year: 2013

DESCRIPTION (provided by applicant): This project is aimed at development of an enzyme immunoassay (EIA) for antibodies to Babesia for use as a clinical diagnostic test. Babesiosis is an emerging tick-borne parasitic disease which may cause severe to fatalillness in immunocompromised or otherwise weakened patients, and may be carried in the blood subclinically in up to 1% of the population in endemic areas. Recent cases of fatal transfusion-transmitted babesiosis have also led to the identification of thispathogen as a significant threat to the blood supply. However, currently no commercial, validated and FDA approved tests are available for B. microti. Babesiosis is currently diagnosed by immunofluorescence staining, microscopy of blood smears, and/or PCR. None of these procedures are easily adaptable to routine clinical laboratory use. We propose to develop a microplate-based ELISA using novel synthetic B. microti antigens licensed to Immunetics that have previously been shown to be diagnostically significant markers. Specificity of the antigens will be assessed in blood donor sera from nonendemic areas and other controls. Assay performance will be evaluated on well-characterized sera from babesiosis patients from both U.S. Northeast and Midwest endemic regions. To identify immunodominant epitopes that may further improve assay sensitivity, we have identified a series of putative Babesia antigenic sequences that will be screened with babesiosis patient serum in an overlapping peptide library format, a strategy that has led to discovery of a number of antigens of diagnostic value. We also propose strategies to identify immunodominant epitopes of other pathogenic Babesia species, B. divergens/MO-1 and B. duncani/WA1. Novel immunodominant epitopes discovered through these strategies will be synthesized as peptide antigens with an appropriate structure for incorporation into current assay formats, which enable combination of multiple distinct peptides in a single-well assay. Once a single-well assay format is developed with sensitivity and specificity characteristics consistent with clinical diagnostic requirements, we will prepare for clinical trials and FDA submission in Phase II. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Babesiosis is an emerging, tick-borne parasitic infection which can produce severe to fatal illness, especially in immunocompromised or weakened patients. However, no FDA approved tests are currently available to aid in clinical diagnosis of this disease. This project will lead to the development, validation and commercial availability of the first simple, accurate and user-friendly diagnostic test for babesiosis.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 598.96K | Year: 2013

DESCRIPTION (provided by applicant): HIV clade C, endemic in sub-Saharan Africa and the Indian subcontinent, is responsible for nearly half of all global HIV infections, and most large-scale HIV vaccine trials are targeted to clade C regions. Unfortunately, the development and trialing of candidate HIV vaccines brings with it the significant risk of vaccine-induced HIV seropositivity (VISP). VISP is defined as the presence of circulating antibodies to HIV vaccine antigens which cross-react with homologous antigens used in conventional HIV immunoassays, leading to a false positive result. In recent HVTN-sponsored HIV vaccine trials, an overall 41.7% of HIV vaccine recipients exhibited VISP. False positive test results can have tragic personal consequences and, from a public health perspective, the anticipated high rate of VISP would make it impossible to monitor effectiveness of an HIV vaccine trial or vaccination campaign, or to correctly diagnose and treat infected individuals. RNA testing, central to current VISP testing algorithms, fails to detect 2-3% of established HIV infections, and its high cost is a burden to vaccine trial budgets and a barrier to use by resource-limited health providers. The goal of the Phase I project is to demonstrate feasibility of a clade C-specific HIV-1 immunoassay ( HIV Selectest ) capable of distinguishing true HIV infection from VISP with high sensitivity and specificity. The rationale behind a clade-specific assay is that it will enable greater detection sensitivity by increasing the number of clade C HIV peptide sequence variants in the space available in the assay well. The project objectives will be achieved through two innovative approaches: 1) clade-specific targeting of assay antigens to improve detection sensitivity and 2) the novel use of database-derived peptide design tools to achieve optimal coverage of HIV variants. Preliminary data have demonstrated that significant gains in detection sensitivity for challenging samples, early infections and overall sample populations are possible through these approaches. Progress will be assessed by ELISA testing of individual antigenic peptides and peptide mixes vs well-characterized serum panels. Through collaborators in research and blood screening laboratories we will acquirepanels of sera from HIV vaccine trials in clade C regions as well as from well-characterized clade C HIV-positive and negative donors. In Phase I we expect to demonstrate feasibility of a clade C HIV Selectest assay capable of distinguishing true HIV infection from VISP, with sensitivity and specificity approaching those of licensed HIV immunoassays when tested on the same target serum panels. In Phase II we will further optimize and scale up the assay and perform prospective and retrospective clinical studies aimed at FDA clearance for use of the Clade C HIV Selectest assay as a cost effective solution to resolve false positives due to VISP in HIV vaccine recipients. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Vaccine-induced seropositivity(VISP) is an undesired result of HIV vaccine trials in which vaccinated individuals develop antibodies to vaccine antigens which can produce false positive results on current HIV tests. VISP can lead to social discrimination as well as confounding the individual's true HIV status and the analysis of vaccine trial results. Numerous HIV vaccine trials are planned for southern Africa where the Clade C genetic strain of HIV predominates. In this project, we will develop a new HIV immunoassay which will for thefirst time discriminate VISP from true infection in vaccine trial participants i Clade C regions of Africa.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 2.80M | Year: 2015

DESCRIPTION provided by applicant Human babesiosis is a malaria like illness caused by infection of red blood cells by the protozoan parasite Babesia microti or related species primarily transmitted to humans through the bite of infected deer ticks Babesiosis can also be transmitted by blood transfusion and is currently acknowledged as the foremost unaddressed infectious risk to the US blood supply Blood donations from B microti endemic areas in the USA can exhibit up to seropositivity and the distribution of seropositivity is expanding rapidly into adjacent states Babesiosis has a wide spectrum of clinical presentation with serious to fatal outcome in immunocompromised individuals which includes many transfusion recipients Undetected Babesia infection in blood donors has been recognized as a serious threat to transfusion safety with transfusion responsible for over cases since and a dozen fatalities since Babesiosis is a andquot rare diseaseandquot by numbers but with potentially serious to fatal impact on those who acquire it which significantly contributes to the health burden of this disease In the absence of other interventions the only viable strategy to prevent the transfusion of B microti contaminated blood units is to screen blood donors for the presence of the parasite However no test for Babesia is currently licensed for blood screening and commercially available Hence there is an urgent and unmet need for blood donor screening to interdict B microti contaminated blood donations This Phase IIb grant will support the development of a Babesia assay based on antigen detection which will supplement the antibody detection ELISA previously developed under the Applicantsandapos prior Phase II grant Babesia parasites secrete antigens into the extracellular medium which may be detected in serum or plasma thus providing a sensitive marker for detection of active infection In collaboration with consortium partner Tufts University applicants have identified immunodominant protein antigens which meet these criteria and have generated specific antibodies suitable for antigen capture immunoassay The antigen capture assay will enable detection of potentially infectious blood donors in the window stage when antibodies are not yet measurable Furthermore it will clear individuals with persistent antibody response due to a previous resolved Babesia infection to donate blood eliminating unnecessary and undesirable donor deferrals The assay will be evaluated on gold standard babesiosis patient samples through collaboration with Yale University and on blood donors through a donor study carried out under IND with consortium partners Blood Systems Research Institute Creative Testing Solutions and New York Blood Center The donor study will support a licensure application to FDA for the Babesia test for blood screening The overall goal is to provide an assay for Babesia microti suitable for high throughput donor screening which will offer the first cost effective intervention to reduce or eliminate the risk of transfusion transmitted babesiosis PUBLIC HEALTH RELEVANCE This project will result in the development clinical trial and FDA submission of the first high throughput screening test for Babesia infection in blood donors which is currently one of the greatest infectious risks of transfusion No test for Babesia is currently licensed by the FDA and commercially available The test to be developed in this project is based on detection of specific Babesia antigens in human plasma samples and will detect donors with asymptomatic window phase Babesia infections mitigating this risk but avoiding false positive results in convalescent individuals which would lead to unnecessary donor deferrals


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 972.24K | Year: 2016

DESCRIPTION provided by applicant Bacterial contamination of platelets is considered the greatest infectious risk of blood product transfusion today at about in platelet units which is several orders of magnitude greater than that of HIV Bacterial contamination at high levels can lead to severe morbidity or mortality in transfusion recipients The American Association of Blood Banks issued directives in and requiring bacterial testing on all platelet units Two recent studies have demonstrated that current FDA approved culture based methods that test for contamination to days prior to transfusion miss a majority of contaminated units The time elapsed between sampling and actual transfusion and the associated risk of bacterial contamination is a fundamental problem that cannot be addressed by current culture based platelet testing A rapid and sensitive point of issue test for bacterial contamination would overcome this problem by providing an assessment of potential contamination immediately prior to transfusion Such a test would be used by a hospital laboratory close to the point of transfusion or by a transfusion center preparing to ship platelet units to a clinical center A rapid test would ideally require less than min have detection sensitivity of CFU mL or better be fully automated and be comparable in cost to current tests BacTx technology developed by Immunetics for detection of bacterial contamination in platelets employs a unique and innovative assay chemistry capable of rapidly detecting both Gram positive and Gram negative bacteria in platelet units The first generation BacTx Bacterial Detection Kit recently received clearance from FDA CBER as a quality control test for pooled leukocyte reduced whole blood derived platelets but this test is not ideally suited for use as a point of issue test due to its length min and complexity requiring centrifugation and accurate pipetting In the Phase I project we successfully demonstrated feasibility of a simple filter based BacTx assay which is rapid andlt min and highly amenable to automation while maintaining the high sensitivity and specificity of the original BacTx test In Phase II we will optimize and configure the rapid test for automated performance and will design build and evaluate prototype instruments and software to run the test The instrument and software development will be carried out in collaboration with engineering partners who have many years of experience in the development of medical test systems with comparable functionality At the conclusion of Phase II we will have developed and validated an integrated rapid BacTx test system ready for clinical studies aimed at k approval Commercialization of this rapid test will enable a paradigm shift in platelet testing and a significant reduction in the number of bacterially contaminated platelet units transfused into critically ill patients Furthermore adopton of the rapid BacTx test could ultimately lead to a change in policy regarding platelets significantly reducing costs for blood banks by allowing an extension of the storage life of platelet units from to days PUBLIC HEALTH RELEVANCE Bacterial contamination of platelets is considered the greatest infectious risk of blood product transfusion today at about in platelet units which is several orders of magnitude greater than that of HIV We have developed a rapid andlt min point of transfusion screening test for detection of bacterial contamination in platelet units that meets or exceeds FDA guidelines We propose to adapt this test to be run by a simple automated device suitable for operation by non specialized personnel in a transfusion center or hospital laboratory Implementation of this rapid test will prevent severe or fatal septic transfusion reactions and lead to better health outcomes for critically ill patients receiving platelet transfusions


Patent
Immunetics, Inc. | Date: 2014-10-14

Assay devices, assay detection systems, and methods comprising same for analytical tests, medical assays, diagnostic tests, medical diagnosis, risk assessment, or quality control purposes are provided. These devices, systems, and methods are designed to be employed at the point of care, such as in emergency rooms, operating rooms, hospital laboratories and other clinical laboratories, doctors offices, in the field, or in any situation in which a rapid and accurate result is desired. The systems and methods process samples, such as clinical, biological, or blood sample, and read data from colorimetric based biochemical assays to provide an indication of the presence or absence of a bacterial, fungal, or viral contaminants therein. The assay devices include an optical reader apparatus and barcode scanner for reading and matching the test results to identification information provided by the barcodes to facilitate ease of tracking compliant and noncompliant samples.


The invention relates to a colorimetric method for detecting bacterial or fungal pathogens by detecting peptidoglycan or (1-3)--D-glucan in a sample.

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