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

Affiliation
United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD 21702, USA. crystal.w.burke.ctr@mail.mil.
Burke, Crystal W.;
Affiliation
United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD 21702, USA. jeffrey.w.froude2.mil@mail.mil.
Froude, Jeffrey W.;
Affiliation
Technische Universität Braunschweig, Institut für Biochemie, Biotechnologie und Bioinformatik, Spielmannstr.7, 38106 Braunschweig, Germany. miethe.sem@icloud.com.
Miethe, Sebastian;
Affiliation
Wehrwissenschaftliches Institut für Schutztechnologien (WIS)-ABC-Schutz, Humboldtstr. 1, 29623 Munster, Germany. BirgitHuelseweh@bundeswehr.org.
Hülseweh, Birgit;
ORCID
0000-0003-3418-6045
Affiliation
Technische Universität Braunschweig, Institut für Biochemie, Biotechnologie und Bioinformatik, Spielmannstr.7, 38106 Braunschweig, Germany. m.hust@tu-bs.de.
Hust, Michael;
Affiliation
United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD 21702, USA. pamela.j.glass.civ@mail.mil.
Glass, Pamela J.

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.

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