SBIR-STTR Award

Recombinant Antigen Diagnostics for Filoviruses
Award last edited on: 11/15/18

Sponsored Program
SBIR
Awarding Agency
NIH : NIAID
Total Award Amount
$3,585,438
Award Phase
2
Solicitation Topic Code
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Principal Investigator
Matthew L Boisen

Company Information

Zalgen Labs LLC

20271 Goldenrod Lane Suite 2083
Germantown, MD 20876
   (504) 444-7047
   admin@zalgenlabs.com
   www.zalgenlabs.com
Location: Single
Congr. District: 06
County: Montgomery

Phase I

Contract Number: 1R43AI088843-01
Start Date: 4/1/10    Completed: 3/31/12
Phase I year
2010
Phase I Amount
$295,123
Viral hemorrhagic fevers (VHFs) are serious, often fatal, illnesses characterized by high fever, damage to the vascular system and multiorgan failure. Our team has successfully produced prototype Lassa virus ELISA that are based on recombinant proteins rather than on reagents that must be produced in high containment laboratories. Under the proposed SBIR, we will now perform critical steps in the preclinical development of commercial recombinant antigen diagnostics for filoviruses, including development of point-of-care lateral flow assays. In MILESTONE 1, we will identify recombinant filovirus proteins (Ebola (EBOV) and Marburg (MARV)) GP, sGP (EBOV only), NP and VP40 appropriate for immunoassay development and initiate production of monoclonal antibodies (MAbs) to these proteins. In MILESTONE 2, we will develop prototype recombinant IgM-, IgG-, and antigen-capture ELISA and lateral flow diagnostics for filoviruses (EBOV and MARV). In the projected MILESTONE 3, we will optimize the scale up and purification of both recombinant filovirus proteins and MAbs, as well as convert to manufacturing with Quality Assurance (QA)/Quality Control (QC) to provide quantities of recombinant proteins and MAbs sufficient for development and testing of commercial assays. In MILESTONE 4, we will perform field testing or BSL-4 testing of the recombinant filovirus ELISA and lateral flow assays to validate and compare with PCR assays. MILESTONE 5 will involve converting manufacturing of the assays to Good Manufacturing Practices (GMP) with QA/QC. The potential use of VHF agents such as EBOV and MARV filoviruses (both are BSL-4 and NIAID Category A agents) as biological weapons directed against civilian or military targets necessitates development of effective, highly sensitive and specific, easy to use, adaptable, and cost-effective diagnostics for public health laboratories, hospital-based clinical laboratories, and point-of-care use. The impact of EBOV in Africa is considerable, and effective diagnostics against these and related viruses can also provide a very significant public health benefit.

Public Health Relevance:
The potential use of VHF agents such as the filoviruses Ebola (EBOV) and Marburg (MARV; both are BSL-4 and NIAID Category A agents) as biological weapons directed against civilian or military targets necessitates development of effective, highly sensitive and specific, easy to use, adaptable, and cost-effective diagnostics for public health laboratories, hospital-based clinical laboratories, and point-of-care use. Under the proposed SBIR we will perform critical steps in preclinical development of commercial recombinant antigen diagnostics for filoviruses, including development of point-of-care lateral flow assays.

Thesaurus Terms:
Atgn; Achievement; Achievement Attainment; Africa; Antigens; Armed Forces Personnel; Assay; Benchmarking; Best Practice Analysis; Bioassay; Biologic Assays; Biological; Biological Assay; Biosynthetic Proteins; Categories; Clinical; Clinical Evaluation; Clinical Testing; Containment; Development; Diagnostic; Disease Outbreaks; Elisa; Enzyme-Linked Immunosorbent Assay; Flr; Failure (Biologic Function); Fever; Filovirus; Gamma Globulin, 19s; Gamma Globulin, 7s; Health Benefit; Hemorrhagic Fevers, Viral; Hyperthermia; Igg; Igm; Immunoassay; Immunoglobulin G; Immunoglobulin M; Laboratories; Lassa Fever; Lassa Virus; Lateral; Military; Military Personnel; Moab, Clinical Treatment; Monoclonal Antibodies; Niaid; National Institute Of Allergy And Infectious Disease; Outbreaks; Phase; Process; Proteins; Public Health; Pyrexia; Quality Control; Reagent; Recombinant Proteins; Recombinants; Sbir; Sbirs (R43/44); Small Business Innovation Research; Small Business Innovation Research Grant; Testing; Vascular System; Viral Hemorrhagic Fevers; Virus; Viruses, General; Base; Clinical Test; Cost; Cost Effective; Design; Designing; Failure; Febrile; Febris; Gene Product; Hemorrhagic Fever; Hospital Laboratories; Immunogen; Monoclonal Antibody Production; Point Of Care; Point-Of-Care Diagnostics; Pre-Clinical; Preclinical; Preclinical Evaluation; Prototype; Public Health Medicine (Field); Public Health Relevance; Quality Assurance; Research Clinical Testing; Scale Up; Weapons

Phase II

Contract Number: 5R43AI088843-02
Start Date: 4/1/10    Completed: 3/31/12
Phase II year
2011
(last award dollars: 2016)
Phase II Amount
$3,290,315

The proposed project will further develop marketable ELISA and lateral-flow immunoassay diagnostics (LFI) in both monoplexed and multiplexed formats for the NIAID category A, BSL-4 filoviruses, and will drive pre-clinical development and validation for these diagnostics. These assays will be used for diagnosis of Ebola virus (EBOV), Sudan virus (SUDV) and Marburg virus (MARV), and will be based on more inexpensive recombinant proteins, rather than reagents that must be produced in high-containment laboratories. We will first scale up production of our existing recombinant filovirus proteins and polyclonal and monoclonal antibodies, in order to meet manufacturing and commercialization requirements. We will next develop second-generation ELISA and LFI prototypes for our existing EBOV, SUDV and MARV antigen detection assays. Third, we will extend the library of available filovirus assays by developing antigen detection tools for the Reston and Bundibugyo viruses. Fourth, we will prepare for commercialization of the assays in both monoplexed multiplexed formats. A multiplexed panel may be ideal for diagnosis as hemorrhagic fevers that are caused by different viruses can present similar symptoms. Antigens from the arenavirus Lassa (LASV), the viral hemorrhagic fever (VHF) most frequently transported out of Africa have already been developed into ELISA and LFI formats by this consortium. Thus, a fifth goal to be accomplished in this project time period is to multiplex LASV antigens with those of the filoviruses in order to develop a broader-scope diagnostic. The resulting multiplexed assays will have utility and marketability for recent travelers who have fallen ill, personnel working in BSL-4 laboratories, in bioterrorism scenarios, and in clinical settings in Africa where these fevers occu naturally. The ultimate goal is to establish a panel of recombinant VHF diagnostics that are easy to use, quick, accurate and cost effective for biodefense and public health purposes. Such diagnostics can be stockpiled to protect civilian and military personnel from viral exposure and release. Viral hemorrhagic fevers are extremely rare in the U.S., but accidental or intentional release could have devastating consequences. Importantly, the simplicity and cost-effectiveness of diagnostics such as these will facilitate the necessary availability of these reagents so that they can be put to immediate use in event of virus exposure or release. Widespread availability of these simple-to-use tests will allow rapid containment of the viruses, and may even serve as a deterrent from using these pathogens as biological weapons.

Public Health Relevance Statement:


Public Health Relevance:
The potential use of the category A filoviruses as biological weapons, and the emergence of these viruses among humans, wildlife and domesticated animals necessitates development of diagnostics for public health laboratories, hospital-based clinical laboratories, and point-of-care use. The availability of highly sensitive and specific, ye adaptable diagnostics in easy-to-use, inexpensive formats would facilitate usage at any location and would allow more rapid identification of these viruses, differential diagnosis from other causes of similar disease, and provision of appropriate treatments, barriers and ring vaccination protocols to contain the disease.

NIH Spending Category:
Biodefense; Biotechnology; Emerging Infectious Diseases; Infectious Diseases; Rare Diseases

Project Terms:
accurate diagnosis; Address; Advanced Development; Affinity; Africa; Antibodies; Antibody Formation; Antigens; Area; Arenavirus; assay development; base; biodefense; Biological; Biological Assay; Bioterrorism; Categories; Cessation of life; Clinical; commercialization; Communication; Complex; Containment; cost effective; cost effectiveness; design; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Differential Diagnosis; Disease; Disease Outbreaks; Domestic Animals; Early Diagnosis; Ebola virus; Enzyme-Linked Immunosorbent Assay; Event; falls; Fever; Filovirus; Frankfurt-Marburg Syndrome Virus; Generations; Goals; Guidelines; Health; hospital laboratories; Human; Human Resources; Immunoassay; In Vitro; Individual; Laboratories; Lassa Fever; Lassa virus; Lateral; Lead; Libraries; Location; Medical; meetings; member; Military Personnel; Monoclonal Antibodies; National Institute of Allergy and Infectious Disease; Nature; Organ failure; pathogen; Performance; Phase; point of care; polyclonal antibody; pre-clinical; preclinical study; Procedures; Process; product development; Production; Proteins; Protocols documentation; prototype; Public Health; quality assurance; Quality Control; Reagent; Recombinant Proteins; Recombinants; Regulatory Pathway; research clinical testing; Reston; Safety; scale up; Specificity; Sudan; Sudan Ebola virus; Symptoms; Technology; Testing; Time; tool; Universities; Vaccination; Validation; Vascular System; Viral; Viral Antibodies; Viral Antigens; Viral Hemorrhagic Fevers; Viral Proteins; Virus; virus identification; weapons; Work