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

Description

Glycoprotein Immunoassay to Measure Protective Humoral Responses to Lassa Vaccine This project will complete the pre clinical development of a Lassa virusLASVglycoprotein immunoassay to measure the protective response to Lassa feverLFvaccinesLF causes endemic febrile illness throughout West Africa and can quickly progress to viral hemorrhagic fever with mortality rates greater thanin high risk groupsLASV is transmitted to humans through exposure to the excreta of its rodent host or direct contact with bodily fluids of an active LF caseThe West African population and non indigenous groups such as deployed US military are at increased risk of zoonotic LF transmissionThis companion diagnostic will fill the unmet need for a standardized assay to measure the humoral response to Lassa virus infection in humans and non human primates and prescreen study candidates and monitor their response to Lassa virus glycoprotein based vaccines now under developmentThe enzyme labeled immunosorbent assayELISAformat test will incorporate highly specific reagents recently developed to advance Lassa fever therapeutics and vaccinesOur proprietary ELISA plate coating will specifically absorb and stabilize trimeric LASV glycoprotein developed at the Scripps Research InstituteThis recombinant glycoprotein has been specially engineered to replicate the neutralizing and nonneutralizing epitopes of LASV currently causing Lassa fever outbreak in West AfricaIdentification of these epitopes was completed through the use of recombinant human monoclonal antibodiesHuMabsderived by researchers at Tulane University and Zalgen Labs from B cells donated by Lassa fever survivors in West AfricaSeveral of these HuMabs have been combined into the therapeutic ArenviramabZalgen Labsand recently shown to completely protect NHPs from fatal inoculations of LASVThe proposed glycoprotein ELISA test will include these HuMabs as reference standard to accurately measure the level of humanand NHPantibody response to LASV vaccineThe first aim of this project will be to complete design optimization of the Lassa GPC Antibody ELISA test including freeze dried reference standardscontrolsand kit packaging for eventual deployment to West African clinical sitesThe second aim of the program will completion of pilot stage kit manufacturing and design validation analytical performance testingThe third aim will be verification of sensitivity and specificity estimates by testing both non human primate and de identified human diagnostic samples from biorepositories in both Sierra Leone and NigeriaOur ultimately goal is a regulatory approved product to support Lassa fever therapeutic and vaccine development studies and assist in the deployment of these lifesaving interventions throughout West Africa and to other at risk groups PROJECT NARRATIVEPublic Health RelevanceLassa feverLFcauses endemic illness throughout West Africa and can quickly progress to viral hemorrhagic fever with mortality rates andgtin high risk groupsThis project will complete the development of a Lassa virusLASVglycoproteinGPimmunoassay to measure the protective response to LF vaccinesThis companion diagnosticLassa GPC Antibody ELISA Testwill fill the unmet need for a standardized assay to measure the humoral response to LASV infection in humans and non human primates and prescreen study candidates and monitor their humoral response to LASV GP based vaccines now under development