Hantaviruses are an emerging family of highly pathogenic viruses that cause 100-200,000 cases of two severe febrile illnesses a year; Hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS). While the annual incidence of infections are relatively low compared to other viral infections, some hantavirus strains are particularly deadly, causing a 35-40% mortality rate in otherwise healthy young adults. In fact, because of their high mortality rates hantaviruses are considered a potential bioterrorism agent by the NIH, CDC and the Department of Defense. Coupled with the fact that there is no virus-specific treatment or globally approved vaccine to protect against infections, these emerging viruses represent a considerable threat to global public health. While there is no virus-specific treatment, evidence indicates that neutralizing antibodies (Abs) can control hantavirus infections in humans. Studies also show that some HFRS and HCPS patients possess Abs that can cross-neutralize heterologous strains. Thus, we hypothesize that some HPCS and HFRS convalescent patients evolve Abs that can broadly neutralize multiple hantavirus strains. Ichor Biologics has developed a platform for the isolation of naturally-occurring human monoclonal Abs (mAbs), which we have used to isolate several hundred hantavirus-specific mAbs from a cohort of HCPS convalescent patients. In characterizing these patients, we observed that some patients developed Abs that recognized a heterologous strain, suggesting that some patients may possess Abs that broadly neutralize multiple hantavirus strains. Therefore, the Product to be developed is a broadly neutralizing Ab(s) therapeutic to treat HCPS and HFRS caused by hantavirus infections. To examine the feasibility of this product, in aim 1 we will screen the hundreds of mAbs previously isolated from HCPS patients for their capacity to neutralize multiple hantavirus strains. This screen will be facilitated by a BSL2-safe, rapid hantavirus neutralization assay developed by Ichor Biologics. Since viruses can acquire mutations that allow them to evade Ab responses, in aim 2, we will determine the functional epitopes bound by any broadly neutralizing Abs in order to identify the Abs that can be combined into a therapeutic cocktail. These studies will determine the potential for developing a broadly neutralizing Ab-based therapeutic from hantavirus convalescent patients and accelerate the commercialization of any therapeutic for use in the clinic. Considering the high safety and efficacy profiles of biologics, plus our strong positioning in the hantavirus space (e.g. strong scientific, legal and business advisors, and Chilean government funding), we are uniquely situated to successfully develop and commercialize a broadly neutralizing Ab(s) therapeutic to treat HCPS and HFRS caused by hantavirus infections.
Public Health Relevance Statement: PROJECT NARRATIVE Ichor Biologics is developing a broadly neutralizing Ab(s) therapeutic to treat the 100,000-200,000 annual cases of HCPS and HFRS caused by hantavirus infections worldwide. Hantavirus infections cause two severe febrile diseases in humans with some virus strains resulting in a 40% mortality rate. Since there is currently no virus-specific treatment or globally-approved vaccine, this emerging family of viruses not only pose a risk as a novel emerging pathogen, but also as a potential bioterrorism threat. This project aims to reduce the public health threat from large outbreaks or bioterrorism attacks.
Project Terms: Acute; Adult; Alanine; Americas; Animal Model; Antibodies; Antibody Response; Antibody Therapy; Area; Asia; base; Binding; Biological; Biological Assay; Biotechnology; Bioterrorism; Businesses; Cardiopulmonary; Centers for Disease Control and Prevention (U.S.); Chilean; Chronic; Clinic; Clinical Trials; cohort; commercial application; commercialization; Communicable Diseases; Computer software; Coupled; cross reactivity; Data; Department of Defense; Development; Disease; Disease Outbreaks; Epitopes; Europe; experimental study; Family; Fever; Funding; Glycoproteins; Goals; Government; Grant; Hantavirus; Hantavirus Infections; Hemorrhagic Fever with Renal Syndrome; high risk; Human; human monoclonal antibodies; Immunoglobulin G; in vivo; in vivo evaluation; Incidence; Industry; Infection; infection risk; innovation; interest; Kidney Diseases; Knowledge; Lead; Legal; Legal patent; Mediating; Mediation; Mesocricetus auratus; molecular modeling; mortality; Mutagenesis; Mutation; neutralizing antibody; novel; off-patent; pathogen; pathogenic virus; Patients; pharmacokinetics and pharmacodynamics; Phase; phase 1 study; Positioning Attribute; programs; prophylactic; Public Health; Radial; Risk; Rodent; Safety; Sampling; Scanning; Serum; Severities; Small Business Innovation Research Grant; Syndrome; Testing; Therapeutic; therapeutic development; Therapeutic Monoclonal Antibodies; Therapeutic Uses; transmission process; Travel; Treatment Efficacy; United States National Institutes of Health; Vaccination; Vaccines; Virus; Virus Diseases; young adult
