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

作者: Ann R. Hunt , Shana Frederickson , Christopher Hinkel , Katherine S. Bowdish , John T. Roehrig

DOI: 10.1099/VIR.0.81925-0

关键词: Nasal administrationBiologyRatónVirusTogaviridaeHumanized antibodyMonoclonal antibodyAntibodyAlphavirusVirology

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

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