Pre-clinical Vaccine Development for Emerging and Re-emerging Infectious Diseases

NIH Pandemic-Era Grants

Pandemic Era Grants

2019

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Principal Investigator: John  Mascola
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2019
Award: $3,639,529
Funding agency: National Institute of Allergy and Infectious Diseases

During the past year, the Virology Core has collaborated with other intramural NIAID labs to develop a MERS-CoV Spike protein subunit vaccine. A vaccine of adjuvanted MERS-CoV Spike protein subunit vaccine confers complete protection from MERS-CoV disease in alpaca and results in reduced and delayed viral shedding in the upper airways of dromedary camels. The data indicate that induction of robust neutralizing humoral immune responses by vaccination of naive animals reduces shedding that potentially could diminish the risk of zoonotic transmission.

We also developed a high-throughput protein binding inhibition assay using image cytometry by selecting a cell type with high DPP4 expression and defining optimal seeding density and protein binding conditions. The ability of monoclonal antibodies to inhibit MERS-CoV S binding was then tested. Binding inhibition results were comparable with those described in previous literature for MERS-CoV spike monomer and showed similar patterns as neutralization results. The coefficient of variation (CV) of our cell-based assay was <10%. The proposed image cytometry method provides an efficient approach for characterizing potential therapeutic antibodies for combating MERS-CoV that compares favorably with current methods. The ability to rapidly determine direct antibody binding to host cells in a high-throughput manner can be applied to study other pathogen-antibody interactions and thus can impact future research on viral pathogens.

Terms: <Adjuvant><Alpaca><Animals><Antibodies><Assay><Binding><Binding Proteins><Bioassay><Biologic Assays><Biological Assay><Camels><Cell Body><Cells><Clinical Treatment Moab><Data><Disease><Disorder><Dromedaries><Emerging Communicable Diseases><Emerging Infectious Diseases><Human><Image Cytometry><Immune response><Immunize><Immunological response><Infection><Ligand Binding Protein><Ligand Binding Protein Gene><Literature><MERS-CoV><Methods><Middle East Respiratory Syndrome><Middle East Respiratory Syndrome Coronavirus><Modern Man><Molecular Interaction><Monoclonal Antibodies><NIAID><National Institute of Allergy and Infectious Disease><Pattern><Protein Binding><Protein Subunits><Risk><Subunit Vaccines><Testing><Therapeutic antibodies><Transmission><Vaccination><Vaccines><Variant><Variation><Viral Shedding><Virus Shedding><Zoonoses><Zoonotic><Zoonotic Infection><base><bound protein><cell type><combat><density><develop a vaccine><development of a vaccine><host response><immunoresponse><mAbs><monomer><pathogen><pathogenic virus><pre-clinical><preclinical><transmission process><vaccine development><vaccine formulation><viral pathogen><virology>