GP38-targeting monoclonal antibodies protect adult mice against lethal Crimean-Congo hemorrhagic fever virus infection.
Sci Adv
; 5(7): eaaw9535, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-31309159
ABSTRACT
Crimean-Congo hemorrhagic fever virus (CCHFV) is an important human pathogen. Limited evidence suggests that antibodies can protect humans against lethal CCHFV disease but the protective efficacy of antibodies has never been evaluated in adult animal models. Here, we used adult mice to investigate the protection provided against CCHFV infection by glycoprotein-targeting neutralizing and non-neutralizing monoclonal antibodies (mAbs). We identified a single non-neutralizing antibody (mAb-13G8) that protected adult type I interferon-deficient mice >90% when treatment was initiated before virus exposure and >60% when administered after virus exposure. Neutralizing antibodies known to protect neonatal mice from lethal CCHFV infection failed to confer protection regardless of immunoglobulin G subclass. The target of mAb-13G8 was identified as GP38, one of multiple proteolytically cleaved glycoproteins derived from the CCHFV glycoprotein precursor polyprotein. This study reveals GP38 as an important antibody target for limiting CCHFV pathogenesis and lays the foundation to develop immunotherapeutics against CCHFV in humans.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Virais
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Vírus da Febre Hemorrágica da Crimeia-Congo
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Anticorpos Neutralizantes
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Anticorpos Monoclonais Murinos
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Febre Hemorrágica da Crimeia
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Anticorpos Antivirais
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article