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Cell Host Microbe. 2015 Jul 8;18(1):86-95. doi: 10.1016/j.chom.2015.06.009.

Isolation and Characterization of Broad and Ultrapotent Human Monoclonal Antibodies with Therapeutic Activity against Chikungunya Virus.

Author information

1
Department of Medicine, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
2
Department of Pediatrics, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
3
Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
4
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
5
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
6
Department of Pediatrics, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
7
Integral Molecular, Philadelphia, PA 19104, USA.
8
Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
9
Department of Pediatrics, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA. Electronic address: james.crowe@vanderbilt.edu.

Erratum in

  • Cell Host Microbe. 2015 Sep 9;18(3):382. Khomadiak, Solomiia [corrected to Khomandiak, Solomiia].

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.

PMID:
26159721
PMCID:
PMC4501771
DOI:
10.1016/j.chom.2015.06.009
[Indexed for MEDLINE]
Free PMC Article

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