Zalgen Labs — Department of Health and Human Services SBIR Phase II: NIAID

Description

DESCRIPTION provided by applicant 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 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 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 we will complete development of LASV multilineage LFI as point of care diagnostics using the Developmental Serum Panel and newly developed antibodies In MILESTONE 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 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 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 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 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