A recombinant humanized monoclonal antibody completely protects mice against lethal challenge with Venezuelan equine encephalitis virus

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Authors
  1. Hu, W-G.
  2. Phelps, A.L.
  3. Jager, S.
  4. Chau, D.
  5. Hu, C.C.
  6. O'Brien, L.M.
  7. Perkins, S.D.
  8. Gates, A.J.
  9. Phillpotts, R.J.
  10. Nagata L.P.
Corporate Authors
Defence R&D Canada - Suffield, Ralston ALTA (CAN);Defence Science and Technology Lab, Porton Down (UK);Waterloo Univ, Waterloo ONT (CAN)
Abstract
A recombinant humanized antibody to Venezuelan equine encephalitis virus (VEEV) was constructed in a monocistronic adenoviral expression vector with a foot-and-mouth-disease virus-derived 2A self-cleavage oligopeptide inserted between the antibody heavy and light chains. After expression in mammalian cells, the heavy and light chains of the humanized antibody (hu1A4A1IgG1-2A) were completely cleaved and properly dimerized. The purified hu1A4A1IgG1-2A retained VEEV binding affinity and neutralizing activity similar to its parental murine antibody. The half-life of hu1A4A1IgG1-2A in mice was approximately 2 days. Passive immunization of hu1A4A1IgG1-2A in mice (50 µ/mouse) 24 hr before or after virulent VEEV challenge provided complete protection, indicating that hu1A4A1IgG1-2A has potent prophylactic and therapeutic effects against VEEV infection.
Keywords
Recombinant humanized antibody;Venezuelan equine encephalitis virus;Prophylactic and therapeutic effects
Report Number
DRDC-SUFFIELD-SL-2009-234 — Scientific Letter
Date of publication
08 Feb 2017
Number of Pages
31
DSTKIM No
CA044644
CANDIS No
804968
Format(s):
Electronic Document(PDF)

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