SBIR-STTR Award

Glycoprotein Immunoassay to Measure Protective Response to Lassa Vaccine
Award last edited on: 3/2/2021

Sponsored Program
SBIR
Awarding Agency
NIH : NIAID
Total Award Amount
$796,134
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: 1R43AI138836-01
Start Date: 3/16/2018    Completed: 2/29/2020
Phase I year
2018
Phase I Amount
$497,084
Glycoprotein Immunoassay to Measure Protective Humoral Responses to Lassa Vaccine This project will complete the pre-clinical development of a Lassa virus (LASV) glycoprotein immunoassay to measure the protective response to Lassa fever (LF) vaccines. LF causes endemic febrile illness throughout West Africa and can quickly progress to viral hemorrhagic fever with mortality rates greater than 50% in high risk groups. LASV is transmitted to humans through exposure to the excreta of its rodent host or direct contact with bodily fluids of an active LF case. The West African population and non-indigenous groups such as deployed US military are at increased risk of zoonotic LF transmission. This 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 development. The enzyme labeled immunosorbent assay (ELISA) format test will incorporate highly specific reagents recently developed to advance Lassa fever therapeutics and vaccines. Our proprietary ELISA plate coating will specifically absorb and stabilize trimeric LASV glycoprotein developed at the Scripps Research Institute. This recombinant glycoprotein has been specially engineered to replicate the neutralizing and non- neutralizing epitopes of LASV currently causing Lassa fever outbreak in West Africa. Identification of these epitopes was completed through the use of recombinant human monoclonal antibodies (HuMabs) derived by researchers at Tulane University and Zalgen Labs from B cells donated by Lassa fever survivors in West Africa. Several of these HuMabs have been combined into the therapeutic Arenviramab-3 (Zalgen Labs) and recently shown to completely protect NHPs from fatal inoculations of LASV. The proposed glycoprotein ELISA test will include these HuMabs as reference standard to accurately measure the level of human (and NHP) antibody response to LASV vaccine. The first aim of this project will be to complete design optimization of the Lassa GPC Antibody ELISA test including freeze-dried reference standards, controls, and kit packaging for eventual deployment to West African clinical sites. The second aim of the program will completion of pilot stage kit manufacturing and design validation analytical performance testing. The 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 Nigeria. Our 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.

Public Health Relevance Statement:
PROJECT NARRATIVE (Public Health Relevance) Lassa fever (LF) causes endemic illness throughout West Africa and can quickly progress to viral hemorrhagic fever with mortality rates >50% in high risk groups. This project will complete the development of a Lassa virus (LASV) glycoprotein (GP) immunoassay to measure the protective response to LF vaccines. This companion diagnostic (Lassa GPC Antibody ELISA Test) will 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.

Project Terms:
Address; Aerosols; Affect; Affinity; Africa; African; Animal Model; Antibodies; Antibody Response; Antigens; Area; assay development; Award; B-Lymphocytes; base; Binding; biobank; Biological Assay; Categories; Cavia; Cessation of life; Clinical; clinical research site; Clinical Sensitivity; Clinical Trials; Combined Vaccines; commercialization; companion diagnostics; Concanavalin A; County; cross reactivity; design; Detection; Development; Diagnostic; Disease; Disease Outbreaks; Ebola virus; effectiveness clinical trial; Engineering; Ensure; Enzymes; Epitopes; Etiology; experimental study; Exposure to; FDA approved; Fever; Formulation; Freeze Drying; Funding; Future; Glycoproteins; Goals; Government; Guidelines; high risk population; Human; human monoclonal antibodies; Immobilization; Immunoassay; Immunoglobulin G; Immunoglobulin M; Immunosorbents; Immunotherapeutic agent; Infection; Institutes; interest; Intervention; Label; Laboratories; Lassa Fever; Lassa virus; Lectin; Life; Liquid substance; Measures; Medical; Memory B-Lymphocyte; Methods; Military Personnel; Molecular Conformation; Monitor; mortality; National Institute of Allergy and Infectious Disease; Nigeria; nonhuman primate; novel; Nucleoproteins; pathogen; Performance; performance tests; Population; pre-clinical; preclinical development; programs; Protocols documentation; public health relevance; Reagent; Recombinants; Recovery; Reference Standards; Reproducibility; Research Institute; Research Personnel; response; Risk; Rodent; Sampling; Sampling Biases; Sensitivity and Specificity; Sierra Leone; Signs and Symptoms; stability testing; Standardization; Structure; Survivors; System; Testing; Therapeutic; therapeutic development; transmission process; United States National Institutes of Health; Universities; vaccine candidate; vaccine development; Vaccines; Validation; validation studies; verification and validation; Vesicular stomatitis Indiana virus; Viral Hemorrhagic Fevers; Virus; Virus Diseases; Zoonoses

Phase II

Contract Number: 5R43AI138836-02
Start Date: 3/16/2018    Completed: 2/29/2020
Phase II year
2019
Phase II Amount
$299,050
Glycoprotein Immunoassay to Measure Protective Humoral Responses to Lassa Vaccine This project will complete the pre-clinical development of a Lassa virus (LASV) glycoprotein immunoassay to measure the protective response to Lassa fever (LF) vaccines. LF causes endemic febrile illness throughout West Africa and can quickly progress to viral hemorrhagic fever with mortality rates greater than 50% in high risk groups. LASV is transmitted to humans through exposure to the excreta of its rodent host or direct contact with bodily fluids of an active LF case. The West African population and non-indigenous groups such as deployed US military are at increased risk of zoonotic LF transmission. This 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 development. The enzyme labeled immunosorbent assay (ELISA) format test will incorporate highly specific reagents recently developed to advance Lassa fever therapeutics and vaccines. Our proprietary ELISA plate coating will specifically absorb and stabilize trimeric LASV glycoprotein developed at the Scripps Research Institute. This recombinant glycoprotein has been specially engineered to replicate the neutralizing and non- neutralizing epitopes of LASV currently causing Lassa fever outbreak in West Africa. Identification of these epitopes was completed through the use of recombinant human monoclonal antibodies (HuMabs) derived by researchers at Tulane University and Zalgen Labs from B cells donated by Lassa fever survivors in West Africa. Several of these HuMabs have been combined into the therapeutic Arenviramab-3 (Zalgen Labs) and recently shown to completely protect NHPs from fatal inoculations of LASV. The proposed glycoprotein ELISA test will include these HuMabs as reference standard to accurately measure the level of human (and NHP) antibody response to LASV vaccine. The first aim of this project will be to complete design optimization of the Lassa GPC Antibody ELISA test including freeze-dried reference standards, controls, and kit packaging for eventual deployment to West African clinical sites. The second aim of the program will completion of pilot stage kit manufacturing and design validation analytical performance testing. The 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 Nigeria. Our 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.

Public Health Relevance Statement:
PROJECT NARRATIVE (Public Health Relevance) Lassa fever (LF) causes endemic illness throughout West Africa and can quickly progress to viral hemorrhagic fever with mortality rates >50% in high risk groups. This project will complete the development of a Lassa virus (LASV) glycoprotein (GP) immunoassay to measure the protective response to LF vaccines. This companion diagnostic (Lassa GPC Antibody ELISA Test) will 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.

NIH Spending Category:
Biodefense; Biotechnology; Clinical Research; Emerging Infectious Diseases; Immunization; Infectious Diseases; Orphan Drug; Prevention; Rare Diseases; Vaccine Related

Project Terms:
Address; Aerosols; Affect; Affinity; Africa; African; Animal Model; Antibodies; Antibody Response; Antigens; Area; assay development; Award; B-Lymphocytes; base; Binding; biobank; Biological Assay; Category A pathogen; Cavia; Cessation of life; Clinical; clinical research site; Clinical Sensitivity; Clinical Trials; Combined Vaccines; commercialization; companion diagnostics; Concanavalin A; County; cross reactivity; design; Detection; Development; Diagnostic; Disease; Disease Outbreaks; Ebola virus; effectiveness clinical trial; Engineering; Ensure; Enzymes; Epitopes; Etiology; experimental study; Exposure to; FDA approved; Fever; Formulation; Freeze Drying; Funding; Future; Glycoproteins; Goals; Government; Guidelines; high risk population; Human; human monoclonal antibodies; Immobilization; Immunoassay; Immunoglobulin G; Immunoglobulin M; Immunosorbents; Immunotherapeutic agent; Infection; Institutes; interest; Intervention; Label; Laboratories; Lassa Fever; Lassa virus; Lectin; Life; Liquid substance; Measures; Medical; Memory B-Lymphocyte; Methods; Military Personnel; Molecular Conformation; Monitor; mortality; National Institute of Allergy and Infectious Disease; Nigeria; nonhuman primate; novel; Nucleoproteins; Performance; performance tests; Population; pre-clinical; preclinical development; programs; Protocols documentation; public health relevance; Reagent; Recombinants; Recovery; Reference Standards; Reproducibility; Research Institute; Research Personnel; response; Risk; Rodent; Sampling; Sampling Biases; Sensitivity and Specificity; Sierra Leone; Signs and Symptoms; stability testing; Standardization; Structure; Survivors; System; Testing; Therapeutic; therapeutic development; transmission process; United States National Institutes of Health; Universities; vaccine candidate; vaccine development; Vaccines; Validation; validation studies; verification and validation; Vesicular stomatitis Indiana virus; Viral Hemorrhagic Fevers; Virus; Virus Diseases; Zoonoses