Characterization of humoral immunity generated against Andes Virus GnGc
Jim Duehr1,2, Danny Noack1, Fatima Amanat1, and Florian Krammer1
1Department of Microbiology and 2Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Hantaviruses are the etiological agent of a number of severe diseases in humans, the most severe of which is Hantavirus Cardiopulmonary Syndrome (HCPS). HCPS has a case fatality rate ranging from 30-50%, and cases are rare, with only ~300 recorded annually in the Americas. Even so, HCPS viruses remain pathogens of major concern due to their potential for misuse as biological weapons, aerosol transmission route, and widespread availability in wild hosts. Despite posing this significant threat to public health, no consistently effective treatment or vaccine is available for hantaviral disease. Here we describe an ongoing effort to identify, characterize, and develop neutralizing and protective antibodies against the glycoprotein complex (Gn and Gc) from Andes Virus, a causative agent of HCPS. When tested for neutralization against a recombinant vesicular stomatitis virus expressing the Andes virus GP (VSV-ANDV) in a plaque reduction neutralization assay, several antibodies led to significant reduction in plaque numbers including four that showed very high neutralizing potency. These antibodies also bind the live Andes virus and have distinct epitopes, most located on the Gn. To elucidate antibody-virus interactions, we generated VSV-ANDV escape mutants and validated them using cross-neutralization assays, ELISAs, and deep sequencing. We have also developed novel recombinant glycoprotein constructs based on most species of the genus orthohantavirus. In combination with these reagents, our antibodies will help drive vaccine development towards key epitopes associated with neutralization and protection, and could themselves be developed into novel point-of-care therapeutics and diagnostics in the developing world.