SBIR-STTR Award

Late-Stage Development Toward Commercialization of Multilineage Point-Of-Care Lassa Fever Diagnostics
Award last edited on: 6/24/16

Sponsored Program
SBIR
Awarding Agency
NIH : NIAID
Total Award Amount
$1,856,094
Award Phase
2
Solicitation Topic Code
-----

Principal Investigator
Luis Manuel Branco

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: 1R44AI115754-01
Start Date: 2/5/15    Completed: 1/31/17
Phase I year
2015
Phase I Amount
$927,590
This project will complete development efforts toward commercialization of multilineage point-of-care Lassa fever diagnostics. Lassa fever (LF) is a severe, often fatal viral hemorrhagic fever (VHF). Because of its high case fatality rate, ability o spread easily by human-human contact, and potential for aerosol release, Lassa virus (LASV), the causative agent of Lassa fever, is classified as a Biosafety Level 4 and NIAID Biodefense category A agent. Our team has successfully produced, validated, CE marked and commercialized recombinant LASV point-of-care lateral flow immunodiagnostics (LFI) for rapid diagnosis of LF caused by lineage IV virus strains. These assays are based on recombinant proteins rather than on reagents that must be produced in high containment laboratories. We have also established robust research programs in Sierra Leone and Nigeria, both endemic areas for LASV, that provide unique clinical and laboratory resources for VHF research. The recombinant immunoassays developed for strains of LASV prevalent in Sierra Leone and surrounding countries will now be reconfigured for the three divergent lineages of LASV in Nigeria - due to lack of sensitivity of lineage IV-specific RDTs for circulating viruses from lineages I-III arising from strain variation. We will now perform critical steps in late-stage development toward commercialization of multilineage point-of- care LF diagnostics. In MILESTONE 1 we will complete development of commercial grade LASV antigen- capture and immunoglobulin M (IgM) and immunoglobulin G (IgG) antibody-capture enzyme-linked immunosorbent assays (ELISA) to lineage I-IV LASV using a Developmental Panel of well-characterized sera. In MILESTONE 2 we will complete development of LASV multilineage LFI as point-of-care diagnostics using the Developmental Serum Panel and newly developed antibodies. In MILESTONE 3 we will convert to manufacturing multilineage recombinant ELISA and LFI under Good Manufacturing Procedures (GMP) to provide quantities of commercial grade diagnostic kits sufficient for preclinical evaluation of design control parameters to achieve benchmarks required for clinical studies, CE marking, and commercialization. In MILESTONE 4 we will optimize scale up and purification of recombinant LASV nucleoprotein (NP) representing currently circulating LASV lineages I-IV, and scale up/purification methods for antibodies to recombinant LASV NP recognizing all currently circulating LASV lineages I-IV. We will then transfer to manufacturing to provide quantities of recombinant proteins and antibodies sufficient for development and production of commercial assays. In MILESTONE 5 we will define and collect positive and negative sera for assay validation from diverse regions across the LASV endemic range of West Africa and elsewhere (European and U.S. controls). We will then validate sensitivity and specificity of multilineage LF recombinant ELISA and LFI. In MILESTONE 6 we will compile Design Validation Report for multilineage reLASV RDT, submission to European Commission for CE marking and to NAFDAC for product registration in Nigeria.

Public Health Relevance Statement:


Public Health Relevance:
The objective of this project is to perform critical steps toward late-stage development and commercialization of multilineage point-of-care Lassa fever diagnostics that rapidly identify the four lineages of LASV (I-IV), the causative agent of Lassa fever (LF), known to circulate in a vast region of West and Central Africa. Lassa fever is a severe and often-fatal hemorrhagic viral disease that is a major biowarfare threat. Unlike many other biothreat agents Lassa virus would be easy to obtain and disseminate to developed countries.

Project Terms:
Achievement; Acute; Aerosols; Africa; Antibodies; Antigens; Area; base; Benchmarking; biodefense; Biological; Biological Assay; Biological Warfare; biothreat; Caring; Case Fatality Rates; Categories; Central Africa; Clinical; Clinical Research; commercialization; Containment; cost effective; Country; design; Developed Countries; Development; Diagnosis; Diagnostic; Enzyme-Linked Immunosorbent Assay; European; Guinea; Health Benefit; Human; Immunoassay; Immunoglobulin G; Immunoglobulin M; Immunological Diagnosis; Industry; Investments; Laboratories; Lassa Fever; Lassa virus; Lateral; Liberia; Medical; Methods; Military Personnel; Monoclonal Antibodies; National Institute of Allergy and Infectious Disease; Nigeria; Nucleoproteins; point of care; point-of-care diagnostics; polyclonal antibody; preclinical evaluation; Procedures; Process; Production; programs; prototype; public health medicine (field); public health relevance; Public Hospitals; rapid diagnosis; Reagent; Recombinant Antibody; Recombinant Proteins; Recombinants; Reporting; Research; Resources; scale up; Sensitivity and Specificity; Serum; Sierra Leone; Staging; Technology; Testing; Validation; Variant; Viral Antigens; Viral Hemorrhagic Fevers; Virus; Virus Diseases; weapons

Phase II

Contract Number: 5R44AI115754-02
Start Date: 2/5/15    Completed: 1/31/17
Phase II year
2016
Phase II Amount
$928,504
This project will complete development efforts toward commercialization of multilineage point-of-care Lassa fever diagnostics. Lassa fever (LF) is a severe, often fatal viral hemorrhagic fever (VHF). Because of its high case fatality rate, ability o spread easily by human-human contact, and potential for aerosol release, Lassa virus (LASV), the causative agent of Lassa fever, is classified as a Biosafety Level 4 and NIAID Biodefense category A agent. Our team has successfully produced, validated, CE marked and commercialized recombinant LASV point-of-care lateral flow immunodiagnostics (LFI) for rapid diagnosis of LF caused by lineage IV virus strains. These assays are based on recombinant proteins rather than on reagents that must be produced in high containment laboratories. We have also established robust research programs in Sierra Leone and Nigeria, both endemic areas for LASV, that provide unique clinical and laboratory resources for VHF research. The recombinant immunoassays developed for strains of LASV prevalent in Sierra Leone and surrounding countries will now be reconfigured for the three divergent lineages of LASV in Nigeria - due to lack of sensitivity of lineage IV-specific RDTs for circulating viruses from lineages I-III arising from strain variation. We will now perform critical steps in late-stage development toward commercialization of multilineage point-of- care LF diagnostics. In MILESTONE 1 we will complete development of commercial grade LASV antigen- capture and immunoglobulin M (IgM) and immunoglobulin G (IgG) antibody-capture enzyme-linked immunosorbent assays (ELISA) to lineage I-IV LASV using a Developmental Panel of well-characterized sera. In MILESTONE 2 we will complete development of LASV multilineage LFI as point-of-care diagnostics using the Developmental Serum Panel and newly developed antibodies. In MILESTONE 3 we will convert to manufacturing multilineage recombinant ELISA and LFI under Good Manufacturing Procedures (GMP) to provide quantities of commercial grade diagnostic kits sufficient for preclinical evaluation of design control parameters to achieve benchmarks required for clinical studies, CE marking, and commercialization. In MILESTONE 4 we will optimize scale up and purification of recombinant LASV nucleoprotein (NP) representing currently circulating LASV lineages I-IV, and scale up/purification methods for antibodies to recombinant LASV NP recognizing all currently circulating LASV lineages I-IV. We will then transfer to manufacturing to provide quantities of recombinant proteins and antibodies sufficient for development and production of commercial assays. In MILESTONE 5 we will define and collect positive and negative sera for assay validation from diverse regions across the LASV endemic range of West Africa and elsewhere (European and U.S. controls). We will then validate sensitivity and specificity of multilineage LF recombinant ELISA and LFI. In MILESTONE 6 we will compile Design Validation Report for multilineage reLASV RDT, submission to European Commission for CE marking and to NAFDAC for product registration in Nigeria.

Public Health Relevance Statement:


Public Health Relevance:
The objective of this project is to perform critical steps toward late-stage development and commercialization of multilineage point-of-care Lassa fever diagnostics that rapidly identify the four lineages of LASV (I-IV), the causative agent of Lassa fever (LF), known to circulate in a vast region of West and Central Africa. Lassa fever is a severe and often-fatal hemorrhagic viral disease that is a major biowarfare threat. Unlike many other biothreat agents Lassa virus would be easy to obtain and disseminate to developed countries.

Project Terms:
Achievement; Acute; Aerosols; Africa; Antibodies; Antigens; Area; base; Benchmarking; biodefense; Biological; Biological Assay; Biological Warfare; biothreat; Caring; Case Fatality Rates; Categories; Central Africa; Clinical; Clinical Research; commercialization; Containment; cost effective; Country; design; Developed Countries; Development; Diagnosis; Diagnostic; Enzyme-Linked Immunosorbent Assay; European; field study; Guinea; Health; Health Benefit; Human; Immunoassay; Immunoglobulin G; Immunoglobulin M; Immunological Diagnosis; Industry; Investments; Laboratories; Lassa Fever; Lassa virus; Lateral; Liberia; Medical; Methods; Military Personnel; Monoclonal Antibodies; National Institute of Allergy and Infectious Disease; Nigeria; Nucleoproteins; point of care; point-of-care diagnostics; polyclonal antibody; preclinical evaluation; Procedures; Process; Production; programs; prototype; public health medicine (field); Public Hospitals; rapid diagnosis; Reagent; Recombinant Antibody; Recombinant Proteins; Recombinants; Reporting; Research; Resources; scale up; Sensitivity and Specificity; Serum; Sierra Leone; Staging; Technology; Testing; Validation; Variant; Viral Antigens; Viral Hemorrhagic Fevers; Virus; Virus Diseases; weapons