A cross-reactive antibody protects against Ross River virus musculoskeletal disease despite rapid neutralization escape in mice.

Arthritogenic alphaviruses cause debilitating musculoskeletal disease and historically have circulated in distinct regions. With the global spread of chikungunya virus (CHIKV), there now is more geographic overlap, which could result in heterologous immunity affecting natural infection or vaccinatio...

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Autores principales:	Julie M Fox, Ling Huang, Stephen Tahan, Laura A Powell, James E Crowe, David Wang, Michael S Diamond
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2020
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8eabbb341c9349a4a8b43532098cfabe
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spelling	oai:doaj.org-article:8eabbb341c9349a4a8b43532098cfabe2021-12-02T19:59:38ZA cross-reactive antibody protects against Ross River virus musculoskeletal disease despite rapid neutralization escape in mice.1553-73661553-737410.1371/journal.ppat.1008743https://doaj.org/article/8eabbb341c9349a4a8b43532098cfabe2020-08-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1008743https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Arthritogenic alphaviruses cause debilitating musculoskeletal disease and historically have circulated in distinct regions. With the global spread of chikungunya virus (CHIKV), there now is more geographic overlap, which could result in heterologous immunity affecting natural infection or vaccination. Here, we evaluated the capacity of a cross-reactive anti-CHIKV monoclonal antibody (CHK-265) to protect against disease caused by the distantly related alphavirus, Ross River virus (RRV). Although CHK-265 only moderately neutralizes RRV infection in cell culture, it limited clinical disease in mice independently of Fc effector function activity. Despite this protective phenotype, RRV escaped from CHK-265 neutralization in vivo, with resistant variants retaining pathogenic potential. Near the inoculation site, CHK-265 reduced viral burden in a type I interferon signaling-dependent manner and limited immune cell infiltration into musculoskeletal tissue. In a parallel set of experiments, purified human CHIKV immune IgG also weakly neutralized RRV, yet when transferred to mice, resulted in improved clinical outcome during RRV infection despite the emergence of resistant viruses. Overall, this study suggests that weakly cross-neutralizing antibodies can protect against heterologous alphavirus disease, even if neutralization escape occurs, through an early viral control program that tempers inflammation.Julie M FoxLing HuangStephen TahanLaura A PowellJames E CroweDavid WangMichael S DiamondPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 16, Iss 8, p e1008743 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Julie M Fox Ling Huang Stephen Tahan Laura A Powell James E Crowe David Wang Michael S Diamond A cross-reactive antibody protects against Ross River virus musculoskeletal disease despite rapid neutralization escape in mice.
description	Arthritogenic alphaviruses cause debilitating musculoskeletal disease and historically have circulated in distinct regions. With the global spread of chikungunya virus (CHIKV), there now is more geographic overlap, which could result in heterologous immunity affecting natural infection or vaccination. Here, we evaluated the capacity of a cross-reactive anti-CHIKV monoclonal antibody (CHK-265) to protect against disease caused by the distantly related alphavirus, Ross River virus (RRV). Although CHK-265 only moderately neutralizes RRV infection in cell culture, it limited clinical disease in mice independently of Fc effector function activity. Despite this protective phenotype, RRV escaped from CHK-265 neutralization in vivo, with resistant variants retaining pathogenic potential. Near the inoculation site, CHK-265 reduced viral burden in a type I interferon signaling-dependent manner and limited immune cell infiltration into musculoskeletal tissue. In a parallel set of experiments, purified human CHIKV immune IgG also weakly neutralized RRV, yet when transferred to mice, resulted in improved clinical outcome during RRV infection despite the emergence of resistant viruses. Overall, this study suggests that weakly cross-neutralizing antibodies can protect against heterologous alphavirus disease, even if neutralization escape occurs, through an early viral control program that tempers inflammation.
format	article
author	Julie M Fox Ling Huang Stephen Tahan Laura A Powell James E Crowe David Wang Michael S Diamond
author_facet	Julie M Fox Ling Huang Stephen Tahan Laura A Powell James E Crowe David Wang Michael S Diamond
author_sort	Julie M Fox
title	A cross-reactive antibody protects against Ross River virus musculoskeletal disease despite rapid neutralization escape in mice.
title_short	A cross-reactive antibody protects against Ross River virus musculoskeletal disease despite rapid neutralization escape in mice.
title_full	A cross-reactive antibody protects against Ross River virus musculoskeletal disease despite rapid neutralization escape in mice.
title_fullStr	A cross-reactive antibody protects against Ross River virus musculoskeletal disease despite rapid neutralization escape in mice.
title_full_unstemmed	A cross-reactive antibody protects against Ross River virus musculoskeletal disease despite rapid neutralization escape in mice.
title_sort	cross-reactive antibody protects against ross river virus musculoskeletal disease despite rapid neutralization escape in mice.
publisher	Public Library of Science (PLoS)
publishDate	2020
url	https://doaj.org/article/8eabbb341c9349a4a8b43532098cfabe
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A cross-reactive antibody protects against Ross River virus musculoskeletal disease despite rapid neutralization escape in mice.

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