Rodent-borne viral outbreaks are increasing in both frequency and impact. As weather patterns evolve, rodent populations are affected and may multiply in areas where increased contact with humans results in infection. Hantaviruses, including Andes (ANDV) and Sin Nombre (SNV), are transmitted through the excreta of infected rodents and, when aerosolized, infect humans. In the Americas, hantavirus infection leads to hantavirus cardiopulmonary syndrome (HCPS), a devastating condition that features rapid onset of pulmonary edema, respiratory failure and cardiogenic shock. Treatment is supportive, not pathogen-targeted, and accordingly, approximately 40% of patients do not survive. Because hantaviruses establish lifelong, asymptomatic infections in their rodent reservoirs, they are highly prevalent in nature and represent a constant threat to humans. For example, SNV is carried by the most abundant mammal in North America, the deer mouse, which has a near ubiquitous distribution throughout the US and Canada. In the case of the South American ANDV, in addition to rodent-to-human transmission, human-to-human transmission occurs, putting not only the patient, but also family members and health care workers at risk. Despite this large potential for infection and the high case fatality rate, there are no FDA-approved treatment options or vaccines available. Hantaviruses are thus classified as NIAID Priority Pathogens and considered potential bioterrorism threats. Our long term goal is to develop an effective therapeutic against HCPS-causing hantaviruses. This proposal seeks to develop human neutralizing antibodies for therapeutic and/or prophylactic treatment of HCPS caused by ANDV. We have assembled a multidisciplinary team of molecular virologists, clinicians, B cell immunologists, and industry partners with experience developing antibody-based therapeutics. The successful development of a potent neutralizing antibody against ANDV has the potential to be a first-line antiviral for the treatment or prevention of HCPS.
Public Health Relevance Statement: Narrative Hantaviruses such as Andes virus (ANDV) are rodent-borne viruses that cause highly lethal disease in humans. No approved drugs or vaccines exist to treat or prevent hantavirus infection. Antiviral antibodies are protective against lethal ANDV infection in animals and humans. We will comprehensively map the antiviral antibodies made in humans during acute ANDV infection and determine which of them strongly neutralize ANDV. The successful development of a potent neutralizing antibody against ANDV has the potential to be a first-line antiviral for the treatment or prevention of HCPS.
NIH Spending Category: Biodefense; Biotechnology; Emerging Infectious Diseases; Immunization; Infectious Diseases; Lung; Prevention
Project Terms: Acute; aerosolized; Affect; American; Americas; Andes Virus; Animals; Antibodies; Antibody Repertoire; Antiviral Agents; Area; B-Lymphocytes; base; Bioterrorism; Canada; Cardiogenic Shock; Cardiopulmonary; Case Fatality Rates; Clinical; Deer Mouse; Dengue Virus; Development; Disease; Disease Outbreaks; experience; Family health status; Family member; Fatality rate; FDA approved; Frequencies; Glycoproteins; Goals; Hamsters; Hantavirus; Hantavirus Infections; Health Personnel; Human; human monoclonal antibodies; Immune Sera; Immunize; immunogenicity; Immunologist; In Vitro; industry partner; infected vector rodent; Infection; Influenza A virus; Lassa Fever; Mammals; Maps; Medicine; Modeling; Molecular; Monoclonal Antibodies; multidisciplinary; National Institute of Allergy and Infectious Disease; Nature; neutralizing antibody; neutralizing monoclonal antibodies; nonhuman primate; North America; pathogen; Pathogenicity; Patients; Pharmaceutical Preparations; Phase; Plasmablast; Population; pre-clinical; preclinical development; prevent; Prevention; Prophylactic treatment; Pulmonary Edema; Respiratory Failure; Risk; Rodent; Serum Immunologic; Sin Nombre virus; South American; Staphylococcus aureus; Syndrome; Therapeutic; Therapeutic antibodies; Toxic effect; transmission process; Treatment Efficacy; Vaccines; Viral; Viral Antibodies; Virus; Virus Diseases; virus envelope; weather patterns; Western Africa; Work
