Research ArticleEMERGING INFECTIONS

Two recombinant human monoclonal antibodies that protect against lethal Andes hantavirus infection in vivo

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Science Translational Medicine  21 Nov 2018:
Vol. 10, Issue 468, eaat6420
DOI: 10.1126/scitranslmed.aat6420

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Antibodies to abrogate Andes hantavirus

Andes hantavirus circulates in rodent reservoirs and can cause hantavirus cardiopulmonary syndrome in humans, resulting in potentially lethal disease; no vaccines or targeted treatments exist. Garrido et al. screened memory B cells from people who had been infected with Andes hantavirus. Antibodies were isolated from one individual with a high viral neutralization capacity. Two of these antibodies were fully protective against disease in a hamster model, even when given several days after infection. These antibodies target distinct epitopes on the viral glycoprotein and could be developed for use alone or as a combination therapy.

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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