Isolation and characterization of broad and ultrapotent human monoclonal antibodies with therapeutic activity against chikungunya virus

Scott A. Smith; Laurie A. Silva; Julie M. Fox; Andrew I. Flyak; Nurgun Kose; Gopal Sapparapu; Solomiia Khomandiak; Alison W. Ashbrook; Kristen M. Kahle; Rachel H. Fong; Sherri Swayne; Benjamin J. Doranz; Charles E. McGee; Mark T. Heise; Pankaj Pal; James D. Brien; S. Kyle Austin; Michael S. Diamond; Terence S. Dermody; James E. Crowe

doi:10.1016/j.chom.2015.06.009

Isolation and characterization of broad and ultrapotent human monoclonal antibodies with therapeutic activity against chikungunya virus

Scott A. Smith, Laurie A. Silva, Julie M. Fox, Andrew I. Flyak, Nurgun Kose, Gopal Sapparapu, Solomiia Khomandiak, Alison W. Ashbrook, Kristen M. Kahle, Rachel H. Fong, Sherri Swayne, Benjamin J. Doranz, Charles E. McGee, Mark T. Heise, Pankaj Pal, James D. Brien, S. Kyle Austin, Michael S. Diamond, Terence S. Dermody, James E. Crowe

Research output: Contribution to journal › Article › peer-review

116 Scopus citations

Abstract

Chikungunya virus (CHIKV) is a mosquito-transmitted RNA virus that causes acute febrile infection associated with polyarthralgia in humans. Mechanisms of protective immunity against CHIKV are poorly understood, and no effective therapeutics or vaccines are available. We isolated and characterized human monoclonal antibodies (mAbs) that neutralize CHIKV infectivity. Among the 30 mAbs isolated, 13 had broad and ultrapotent neutralizing activity (IC50 < 10 ng/ml), and all of these mapped to domain A of the E2 envelope protein. Potent inhibitory mAbs blocked post-attachment steps required for CHIKV membrane fusion, and several were protective in a lethal challenge model in immunocompromised mice, even when administered at late time points after infection. These highly protective mAbs could be considered for prevention or treatment of CHIKV infection, and their epitope location in domain A of E2 could be targeted for rational structure- based vaccine development.

Original language	English
Pages (from-to)	86-95
Number of pages	10
Journal	Cell Host and Microbe
Volume	18
Issue number	1
DOIs	https://doi.org/10.1016/j.chom.2015.06.009
State	Published - 2015

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc.

ASJC Scopus subject areas

Parasitology
Microbiology
Virology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.chom.2015.06.009

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Smith, S. A., Silva, L. A., Fox, J. M., Flyak, A. I., Kose, N., Sapparapu, G., Khomandiak, S., Ashbrook, A. W., Kahle, K. M., Fong, R. H., Swayne, S., Doranz, B. J., McGee, C. E., Heise, M. T., Pal, P., Brien, J. D., Austin, S. K., Diamond, M. S., Dermody, T. S., & Crowe, J. E. (2015). Isolation and characterization of broad and ultrapotent human monoclonal antibodies with therapeutic activity against chikungunya virus. Cell Host and Microbe, 18(1), 86-95. https://doi.org/10.1016/j.chom.2015.06.009

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title = "Isolation and characterization of broad and ultrapotent human monoclonal antibodies with therapeutic activity against chikungunya virus",

abstract = "Chikungunya virus (CHIKV) is a mosquito-transmitted RNA virus that causes acute febrile infection associated with polyarthralgia in humans. Mechanisms of protective immunity against CHIKV are poorly understood, and no effective therapeutics or vaccines are available. We isolated and characterized human monoclonal antibodies (mAbs) that neutralize CHIKV infectivity. Among the 30 mAbs isolated, 13 had broad and ultrapotent neutralizing activity (IC50 < 10 ng/ml), and all of these mapped to domain A of the E2 envelope protein. Potent inhibitory mAbs blocked post-attachment steps required for CHIKV membrane fusion, and several were protective in a lethal challenge model in immunocompromised mice, even when administered at late time points after infection. These highly protective mAbs could be considered for prevention or treatment of CHIKV infection, and their epitope location in domain A of E2 could be targeted for rational structure- based vaccine development.",

author = "Smith, {Scott A.} and Silva, {Laurie A.} and Fox, {Julie M.} and Flyak, {Andrew I.} and Nurgun Kose and Gopal Sapparapu and Solomiia Khomandiak and Ashbrook, {Alison W.} and Kahle, {Kristen M.} and Fong, {Rachel H.} and Sherri Swayne and Doranz, {Benjamin J.} and McGee, {Charles E.} and Heise, {Mark T.} and Pankaj Pal and Brien, {James D.} and Austin, {S. Kyle} and Diamond, {Michael S.} and Dermody, {Terence S.} and Crowe, {James E.}",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

doi = "10.1016/j.chom.2015.06.009",

language = "English",

volume = "18",

pages = "86--95",

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Smith, SA, Silva, LA, Fox, JM, Flyak, AI, Kose, N, Sapparapu, G, Khomandiak, S, Ashbrook, AW, Kahle, KM, Fong, RH, Swayne, S, Doranz, BJ, McGee, CE, Heise, MT, Pal, P, Brien, JD, Austin, SK, Diamond, MS, Dermody, TS & Crowe, JE 2015, 'Isolation and characterization of broad and ultrapotent human monoclonal antibodies with therapeutic activity against chikungunya virus', Cell Host and Microbe, vol. 18, no. 1, pp. 86-95. https://doi.org/10.1016/j.chom.2015.06.009

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T1 - Isolation and characterization of broad and ultrapotent human monoclonal antibodies with therapeutic activity against chikungunya virus

AU - Smith, Scott A.

AU - Silva, Laurie A.

AU - Fox, Julie M.

AU - Flyak, Andrew I.

AU - Kose, Nurgun

AU - Sapparapu, Gopal

AU - Khomandiak, Solomiia

AU - Ashbrook, Alison W.

AU - Kahle, Kristen M.

AU - Fong, Rachel H.

AU - Swayne, Sherri

AU - Doranz, Benjamin J.

AU - McGee, Charles E.

AU - Heise, Mark T.

AU - Pal, Pankaj

AU - Brien, James D.

AU - Austin, S. Kyle

AU - Diamond, Michael S.

AU - Dermody, Terence S.

AU - Crowe, James E.

PY - 2015

Y1 - 2015

N2 - Chikungunya virus (CHIKV) is a mosquito-transmitted RNA virus that causes acute febrile infection associated with polyarthralgia in humans. Mechanisms of protective immunity against CHIKV are poorly understood, and no effective therapeutics or vaccines are available. We isolated and characterized human monoclonal antibodies (mAbs) that neutralize CHIKV infectivity. Among the 30 mAbs isolated, 13 had broad and ultrapotent neutralizing activity (IC50 < 10 ng/ml), and all of these mapped to domain A of the E2 envelope protein. Potent inhibitory mAbs blocked post-attachment steps required for CHIKV membrane fusion, and several were protective in a lethal challenge model in immunocompromised mice, even when administered at late time points after infection. These highly protective mAbs could be considered for prevention or treatment of CHIKV infection, and their epitope location in domain A of E2 could be targeted for rational structure- based vaccine development.

AB - Chikungunya virus (CHIKV) is a mosquito-transmitted RNA virus that causes acute febrile infection associated with polyarthralgia in humans. Mechanisms of protective immunity against CHIKV are poorly understood, and no effective therapeutics or vaccines are available. We isolated and characterized human monoclonal antibodies (mAbs) that neutralize CHIKV infectivity. Among the 30 mAbs isolated, 13 had broad and ultrapotent neutralizing activity (IC50 < 10 ng/ml), and all of these mapped to domain A of the E2 envelope protein. Potent inhibitory mAbs blocked post-attachment steps required for CHIKV membrane fusion, and several were protective in a lethal challenge model in immunocompromised mice, even when administered at late time points after infection. These highly protective mAbs could be considered for prevention or treatment of CHIKV infection, and their epitope location in domain A of E2 could be targeted for rational structure- based vaccine development.

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SN - 1931-3128

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JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 1

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Isolation and characterization of broad and ultrapotent human monoclonal antibodies with therapeutic activity against chikungunya virus

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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