Human-Like Neutralizing Antibodies Protect Mice from Aerosol Exposure with Western Equine Encephalitis Virus

Viruses. 2018 Mar 24;10(4):147. doi: 10.3390/v10040147.

Abstract

Western equine encephalitis virus (WEEV) causes symptoms in humans ranging from mild febrile illness to life-threatening encephalitis, and no human medical countermeasures are licensed. A previous study demonstrated that immune serum from vaccinated mice protected against lethal WEEV infection, suggesting the utility of antibodies for pre- and post-exposure treatment. Here, three neutralizing and one binding human-like monoclonal antibodies were evaluated against WEEV aerosol challenge. Dose-dependent protection was observed with two antibodies administered individually, ToR69-3A2 and ToR68-2C3. In vitro neutralization was not a critical factor for protection in this murine model, as ToR69-3A2 is a strong neutralizing antibody, and ToR68-2C3 is a non-neutralizing antibody. This result highlights the importance of both neutralizing and non-neutralizing antibodies in the protection of mice from WEEV lethality.

Keywords: NHP antibodies; aerosol challenge; alphavirus; antibody engineering; monoclonal antibody (mAb); passive vaccine; scFv-Fc; western equine encephalitis virus (WEEV).

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aerosols
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Neutralizing / administration & dosage
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / administration & dosage
  • Antibodies, Viral / immunology*
  • Disease Models, Animal
  • Encephalitis Virus, Western Equine / immunology*
  • Encephalomyelitis, Equine / immunology*
  • Encephalomyelitis, Equine / mortality
  • Encephalomyelitis, Equine / prevention & control*
  • Encephalomyelitis, Equine / virology
  • Immunization
  • Mice
  • Morbidity
  • Mortality

Substances

  • Aerosols
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral