Therapeutic administration of a recombinant human monoclonal antibody reduces the severity of chikungunya virus disease in rhesus macaques

被引：49

作者：

Broeckel, Rebecca ^{[1
]}

Fox, Julie M. ^{[2
,3
,4
]}

Haese, Nicole ^{[1
]}

Kreklywich, Craig N. ^{[1
]}

Sukulpovi-Petty, Soila ^{[2
,3
,4
]}

Legasse, Alfred ^{[5
]}

Smith, Patricia P. ^{[1
]}

Denton, Michael ^{[1
]}

Corvey, Carsten ^{[6
]}

Krishnan, Shiv ^{[6
]}

Colgin, Lois M. A. ^{[7
]}

Ducore, Rebecca M. ^{[7
]}

Lewis, Anne D. ^{[7
]}

Axthelm, Michael K. ^{[1
,5
]}

Mandron, Marie ^{[8
]}

Cortez, Pierre ^{[8
]}

Rothblatt, Jonathan ^{[6
]}

Rao, Ercole ^{[8
]}

Focken, Ingo ^{[8
]}

Carter, Kara ^{[6
]}

Sapparapau, Gopal ^{[9
,10
]}

Crowe, James E., Jr. ^{[9
,10
,11
]}

Diamond, Michael S. ^{[2
,3
,4
,11
]}

Streblow, Daniel N. ^{[1
,5
]}

机构：

[1] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA

[2] Washington Univ, Dept Med, Sch Med, St Louis, MO USA

[3] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA

[4] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO USA

[5] Oregon Natl Primate Res Ctr, Div Pathobiol & Immunol, Beaverton, OR 97006 USA

[6] Sanofi, Cambridge, MA USA

[7] Oregon Natl Primate Res Ctr, Pathol Serv Unit, Div Comparat Med, Beaverton, OR USA

[8] Sanofi, Marcy Letoile, France

[9] Vanderbilt Univ, Dept Pediat & Pathol, 221 Kirkland Hall, Nashville, TN 37235 USA

[10] Vanderbilt Univ, Dept Microbiol, Nashville, TN USA

[11] Vanderbilt Univ, Dept Immunol, Nashville, TN USA

来源：

PLOS NEGLECTED TROPICAL DISEASES | 2017年 / 11卷 / 06期

关键词：

REUNION ISLAND; BINARY ETHYLENIMINE; INFECTION; VACCINE; ARTHRALGIA; OUTBREAK; EPIDEMIC; IMMUNITY; TARGETS; FEVER;

D O I：

10.1371/journal.pntd.0005637

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

Chikungunya virus (CHIKV) is a mosquito-borne virus that causes a febrile syndrome in humans associated with acute and chronic debilitating joint and muscle pain. Currently no licensed vaccines or therapeutics are available to prevent or treat CHIKV infections. We recently isolated a panel of potently neutralizing human monoclonal antibodies (mAbs), one (4N12) of which exhibited prophylactic and post-exposure therapeutic activity against CHIKV in immunocompromised mice. Here, we describe the development of an engineered CHIKV mAb, designated SVIR001, that has similar antigen binding and neutralization profiles to its parent, 4N12. Because therapeutic administration of SVIR001 in immunocompetent mice significantly reduced viral load in joint tissues, we evaluated its efficacy in a rhesus macaque model of CHIKV infection. Rhesus macaques that were treated after infection with SVIR001 showed rapid elimination of viremia and less severe joint infiltration and disease compared to animals treated with SVIR002, an isotype control mAb. SVIR001 reduced viral burden at the site of infection and at distant sites and also diminished the numbers of activated innate immune cells and levels of pro-inflammatory cytokines and chemokines. SVIR001 therapy; however, did not substantively reduce the induction of CHIKV-specific B or T cell responses. Collectively, these results show promising therapeutic activity of a human anti-CHIKV mAb in rhesus macaques and provide proof-of-principle for its possible use in humans to treat active CHIKV infections.

引用

页数：25

共 55 条

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