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

Rebecca Broeckel, Julie M. Fox, Nicole Haese, Craig N. Kreklywich, Soila Sukulpovi-Petty, Alfred Legasse, Patricia P. Smith, Michael Denton, Carsten Corvey, Shiv Krishnan, Lois Colgin, Rebecca Ducore, Anne Lewis, Michael Axthelm, Marie Mandron, Pierre Cortez, Jonathan Rothblatt, Ercole Rao, Ingo Focken, Kara CarterGopal Sapparapau, James E. Crowe, Michael S. Diamond, Daniel Streblow

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere0005637
JournalPLoS Neglected Tropical Diseases
Volume11
Issue number6
DOIs
StatePublished - Jun 19 2017

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Chikungunya virus
Virus Diseases
Macaca mulatta
Monoclonal Antibodies
Viral Load
Therapeutics
Joint Diseases
Viremia
Myalgia
Arthralgia
Infection
Culicidae
Chemokines
Human Activities
B-Lymphocytes
Fever
Vaccines
Joints
Cytokines
Viruses

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Therapeutic administration of a recombinant human monoclonal antibody reduces the severity of chikungunya virus disease in rhesus macaques. / Broeckel, Rebecca; Fox, Julie M.; Haese, Nicole; Kreklywich, Craig N.; Sukulpovi-Petty, Soila; Legasse, Alfred; Smith, Patricia P.; Denton, Michael; Corvey, Carsten; Krishnan, Shiv; Colgin, Lois; Ducore, Rebecca; Lewis, Anne; Axthelm, Michael; Mandron, Marie; Cortez, Pierre; Rothblatt, Jonathan; Rao, Ercole; Focken, Ingo; Carter, Kara; Sapparapau, Gopal; Crowe, James E.; Diamond, Michael S.; Streblow, Daniel.

In: PLoS Neglected Tropical Diseases, Vol. 11, No. 6, e0005637, 19.06.2017.

Research output: Contribution to journalArticle

Broeckel, R, Fox, JM, Haese, N, Kreklywich, CN, Sukulpovi-Petty, S, Legasse, A, Smith, PP, Denton, M, Corvey, C, Krishnan, S, Colgin, L, Ducore, R, Lewis, A, Axthelm, M, Mandron, M, Cortez, P, Rothblatt, J, Rao, E, Focken, I, Carter, K, Sapparapau, G, Crowe, JE, Diamond, MS & Streblow, D 2017, 'Therapeutic administration of a recombinant human monoclonal antibody reduces the severity of chikungunya virus disease in rhesus macaques', PLoS Neglected Tropical Diseases, vol. 11, no. 6, e0005637. https://doi.org/10.1371/journal.pntd.0005637
Broeckel, Rebecca ; Fox, Julie M. ; Haese, Nicole ; Kreklywich, Craig N. ; Sukulpovi-Petty, Soila ; Legasse, Alfred ; Smith, Patricia P. ; Denton, Michael ; Corvey, Carsten ; Krishnan, Shiv ; Colgin, Lois ; Ducore, Rebecca ; Lewis, Anne ; Axthelm, Michael ; Mandron, Marie ; Cortez, Pierre ; Rothblatt, Jonathan ; Rao, Ercole ; Focken, Ingo ; Carter, Kara ; Sapparapau, Gopal ; Crowe, James E. ; Diamond, Michael S. ; Streblow, Daniel. / Therapeutic administration of a recombinant human monoclonal antibody reduces the severity of chikungunya virus disease in rhesus macaques. In: PLoS Neglected Tropical Diseases. 2017 ; Vol. 11, No. 6.
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AU - Sukulpovi-Petty, Soila

AU - Legasse, Alfred

AU - Smith, Patricia P.

AU - Denton, Michael

AU - Corvey, Carsten

AU - Krishnan, Shiv

AU - Colgin, Lois

AU - Ducore, Rebecca

AU - Lewis, Anne

AU - Axthelm, Michael

AU - Mandron, Marie

AU - Cortez, Pierre

AU - Rothblatt, Jonathan

AU - Rao, Ercole

AU - Focken, Ingo

AU - Carter, Kara

AU - Sapparapau, Gopal

AU - Crowe, James E.

AU - Diamond, Michael S.

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