Two Recombinant Human Monoclonal Antibodies That Protect Against Lethal Andes Hantavirus Infection in Vivo

Overview

Journal Sci Transl Med

Specialties General Medicine
Science

Date 2018 Nov 23

PMID 30463919

Citations 32

Authors

Jose L Garrido

Joseph Prescott

Mario Calvo

Felipe Bravo

Raymond Alvarez

Alexis Salas

Raul Riquelme

Maria L Rioseco

Brandi N Williamson

Elaine Haddock

Heinz Feldmann

Maria I Barria

Affiliations

Soon will be listed here.

Abstract

Andes hantavirus (ANDV) is an etiologic agent of hantavirus cardiopulmonary syndrome (HCPS), a severe disease characterized by fever, headache, and gastrointestinal symptoms that may progress to hypotension, pulmonary failure, and cardiac shock that results in a 25 to 40% case-fatality rate. Currently, there is no specific treatment or vaccine; however, several studies have shown that the generation of neutralizing antibody (Ab) responses strongly correlates with survival from HCPS in humans. In this study, we screened 27 ANDV convalescent HCPS patient sera for their capacity to bind and neutralize ANDV in vitro. One patient who showed high neutralizing titer was selected to isolate ANDV-glycoprotein (GP) Abs. ANDV-GP-specific memory B cells were single cell sorted, and recombinant immunoglobulin G antibodies were cloned and produced. Two monoclonal Abs (mAbs), JL16 and MIB22, potently recognized ANDV-GPs and neutralized ANDV. We examined the post-exposure efficacy of these two mAbs as a monotherapy or in combination therapy in a Syrian hamster model of ANDV-induced HCPS, and both mAbs protected 100% of animals from a lethal challenge dose. These data suggest that monotherapy with mAb JL16 or MIB22, or a cocktail of both, could be an effective post-exposure treatment for patients infected with ANDV-induced HCPS.

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