Characterization of the Humoral Immune Response in Rats and Non-human Primates Exposed to Aerosolized Virulent Rift Valley Fever Virus

Rift Valley fever virus (RVFV) is an emerging zoonotic pathogen that has been responsible for extensive and devastating outbreaks of disease in both humans and livestock throughout Africa and the Arabian Peninsula. Humans infected with RVFV can recover after a brief febrile illness or go on to develop a more severe outcome including encephalitis, hepatitis, or hemorrhagic fever. Although human transmission primarily occurs through direct interaction with sick animals, inhalational infection can occur, making aerosolized RVFV a plausible bioweapon with potential for severe public health consequences. RVFV does not have a well-characterized rat or non-human primate (NHP) model for aerosol challenge. Animal models are essential for the testing of medical countermeasures, with knowledge of the host immune response aiding in their development. To further our understanding of the role that antibodies play in shaping the outcome of respiratory disease, inbred rats and non-human primates were exposed to aerosolized RVFV. Wistar-Furth, ACI, and Lewis rats were challenged in median lethal dose and serial sacrifice studies from which samples were tested to determine the robustness and timing of the IgG response. Wistar-Furth rats succumbed to hepatic disease shortly after infection, and never mounted a detectable antibody response. ACI and Lewis rats developed neurologic disease, with IgG appearing 6 d.p.i. and potentially influencing host survivability. To investigate the significance of the humoral response during respiratory infection of NHPs, cynomolgus macaques, rhesus macaques, African Green monkeys, and marmosets, were inoculated with RVFV via aerosol route, with blood samples taken at several time points. Cynomolgus and rhesus species were not sensitive to developing disease, but elicited strong IgG and neutralizing antibodies in response to inoculation. AGMs and marmosets showed moderate to high susceptibility to neurologic disease, even in the presence of extremely high titers of neutralizing antibodies. Further immunity studies are pertinent to better comprehend these host-pathogen interactions after RVFV aerosol challenge