Analysis of Recombinant Cedar Virus Infection and Cross-Protection Against Related Henipaviruses in African Green Monkeys

Cedar virus (CedV), related to the highly pathogenic bat-borne henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), is non-pathogenic in small animal models, likely due to the inability to produce interferon-antagonist proteins. We evaluated the pathogenesis of recombinant CedV (rCedV) in the African green monkey (AGM) model and determined if prior infection conferred cross-protective immunity against a lethal challenge with NiV Bangladesh (NiV-B) or HeV. AGMs infected with rCedV remained asymptomatic, with no clinical signs of disease or detectable viremia. The rCedV infected animals developed homologous neutralizing antibody responses that failed to cross-neutralize NiV-B or HeV. At 42 days post-rCedV infection, AGMs were challenged with a lethal dose of NiV-B or HeV, and prior infection with rCedV failed to protect against NiV-B challenge, with all animals succumbing to NiV-B. Similarly, rCedV infection did not confer consistent protection against HeV, with 2/4 animals succumbing to lethal HeV. These findings confirm that CedV is non-pathogenic in the AGM model of NiV and HeV infection, justifying its classification as a BSL-2 agent. The findings also demonstrate that rCedV does not elicit a cross-protective immune response to prevent lethal disease from either NiV-B or HeV highlighting significant immunological differences between CedV and the pathogenic henipaviruses.