A single dose of purified human antibody from transchromosomic bovines mitigates aerosolized Venezuelan equine encephalitis virus disease in cynomolgus macaques

Abstract

Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne RNA virus that causes low mortality but high morbidity in humans. In addition to natural outbreaks, there is potential for exposure to VEEV via aerosolized virus particles. Currently there are no FDA-licensed vaccines or antiviral therapies for VEEV. We previously demonstrated that high titer anti-VEEV human antibody preparations derived from the plasma of hyperimmunized transchromosomic (Tc) bovines provided significant protection to mice from subcutaneous and aerosol challenge with virulent VEEV (Gardner et al., J. Virol. , 91:e00226-17, 2017). In the current studies we utilized the cynomolgus macaque primate model of VEEV infection, challenging some treatment groups with either a IA/B clade virus or a IC clade virus, each derived from a cDNA clone. Animals were treated with liquid or lyophilized transchromosomic bovine polyclonal antibody (TcpAb) preparations via intravenous (IV) or intranasal (IN) routes. Single dose prophylactic (24 hr before challenge) treatment with the liquid TcpAb given IV yielded significant reduction in the magnitude and/or extent of febrile responses and eliminated or greatly reduced serum infectious viremia versus control after aerosol challenge with VEEV regardless of subtype. Therapeutic (24 hr after challenge) treatment showed similar results with the IA/B virus. However, IN treatment alone with lyophilized TcpAb was ineffective against the IC virus. These results indicate that IV treatment with the TcpAb is effective in reducing VEEV disease severity in non-human primates and may be a useful single treatment strategy for infections with this emerging virus.