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A humanized murine monoclonal antibody protects mice either before or after challenge with virulent Venezuelan equine encephalomyelitis virus

¹ Arbovirus Diseases Branch, Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, US Department of Health and Human Services, PO Box 2087, Fort Collins, CO 80522, USA
² Alexion Antibody Technologies, San Diego, CA 92121, USA

Correspondence
Ann R. Hunt
arh4{at}cdc.gov

A humanized monoclonal antibody (mAb) has been developed and its potential to protect from or cure a Venezuelan equine encephalomyelitis virus (VEEV) infection was evaluated. The VEEV-neutralizing, protective murine mAb 3B4C-4 was humanized using combinatorial antibody libraries and phage-display technology. Humanized VEEV-binding Fabs were evaluated for virus-neutralizing capacity, then selected Fabs were converted to whole immunoglobulin (Ig) G1, and stable cell lines were generated. The humanized mAb Hy4-26C, designated Hy4 IgG, had virus-neutralizing capacity similar to that of 3B4C-4. Passive antibody protection studies with purified Hy4 IgG were performed in adult Swiss Webster mice. As little as 100 ng Hy4 IgG protected 90 % of mice challenged with 100 intraperitoneal (i.p.) mean morbidity (MD₅₀) doses of virulent VEEV (Trinidad donkey) 24 h after antibody transfer; also, 500 µg Hy4 IgG protected 80 % of mice inoculated with 100 intranasal MD₅₀ doses of VEEV. Moreover, 10 µg passive Hy4 IgG protected 70 % of mice from a VEEV challenge dose as great as 10⁷ i.p. MD₅₀. Hy4 IgG also protected mice from challenge with another epizootic VEEV variety, 1C (P676). Importantly, therapeutic administration of the humanized mAb to mice already infected with VEEV cured 90 % of mice treated with Hy4 IgG within 1 h of VEEV inoculation and 75 % of mice treated 24 h after virus infection.

Published online ahead of print on 7 June 2006 as DOI 10.1099/vir.0.81925-0.

The GenBank/EMBL/DDBJ accession numbers for the sequences reported in this paper are DQ487205–DQ487208.

Supplementary tables are available in JGV Online.

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