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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / isolation & purification
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / isolation & purification
  • Antibodies, Neutralizing / therapeutic use
  • Antibodies, Viral / immunology*
  • Antibodies, Viral / isolation & purification
  • Antibodies, Viral / therapeutic use*
  • Chemoprevention / methods
  • Chikungunya Fever / therapy*
  • Chikungunya virus / immunology*
  • Chikungunya virus / physiology
  • Disease Models, Animal
  • Humans
  • Immunization, Passive / methods*
  • Inhibitory Concentration 50
  • Mice
  • Protein Binding
  • Survival Analysis
  • Treatment Outcome
  • Viral Envelope Proteins / immunology
  • Virus Internalization / drug effects


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Viral Envelope Proteins