Antigenic mapping and functional characterization of human New World hantavirus neutralizing antibodies

• DOI: 10.7554/elife.81743
• Publication Date: 2023-03-27T10:15:42Z
• Authors: Taylor B Engdahl; Elad Binshtein; Rebecca L Brocato; Natalia A Kuzmina; Lucia M Principe; Steven A Kwilas; Robert K Kim; Nathaniel S Chapman; Monique S Porter; Pablo Guardado-Calvo; Félix A Rey; Laura S Handal; Summer M Diaz; Irene A Zagol-Ika...; Minh H Tran; W Hayes McDonald; Jens Meiler; Joseph X Reidy; Andrew Trivette; Alexander Bukreyev; Jay W Hooper; James E Crowe
• Keywords: Hantavirus Infection; Hantavirus pulmonary syndrome; Hantaan virus; Epitope mapping

Hantaviruses are high-priority emerging pathogens carried by rodents and transmitted to humans aerosolized excreta or, in rare cases, person-to-person contact. While infections relatively rare, mortality rates range from 1 40% depending on the hantavirus species. There currently no FDA-approved vaccines or therapeutics for hantaviruses, only treatment infection is supportive care respiratory kidney failure. Additionally, human humoral immune response incompletely understood, especially location of major antigenic sites viral glycoproteins conserved neutralizing epitopes. Here, we report mapping functional characterization four antibodies. The broadly antibody SNV-53 targets an interface between Gn/Gc, neutralizes through fusion inhibition cross-protects against Old World species Hantaan virus when administered pre- post-exposure. Another broad antibody, SNV-24, also but domain I Gc demonstrates weak activity authentic hantaviruses. ANDV-specific, antibodies (ANDV-5 ANDV-34) neutralize attachment blocking protect cardiopulmonary syndrome (HCPS) animals target two different faces head Gn. Determining will contribute further therapeutic development hantavirus-related diseases inform design new protective vaccines.