Postexposure Protection Against Marburg Haemorrhagic Fever with Recombinant Vesicular Stomatitis Virus Vectors in Non-Human Primates: An Efficacy Assessment

摘要

Effective countermeasures are urgently needed to prevent and treat infections caused by highly pathogenic and biological threat agents such as Marburg virus (MARV). We aimed to test the efficacy of a replication-competent vaccine based on attenuated recombinant vesicular stomatitis virus (rVSV), as a postexposure treatment for MARV haemorrhagic fever. We used a rhesus macaque model of MARV haemorrhagic fever that produced 100% lethality. We administered rVSV vectors expressing the MARV Musoke strain glycoprotein to five macaques 20- 30 min after a high-dose lethal injection of homologous MARV. Three animals were MARV-positive controls and received non-specific rVSV vectors. We tested for viraemia, undertook analyses for haematology and serum biochemistry, and measured humoral and cellular immune responses. All five rhesus monkeys that were treated with the rVSV MARV vectors as a postexposure treatment survived a high-dose lethal challenge of MARV for at least 80 days. None of these five animals developed clinical symptoms consistent with MARV haemorrhagic fever. All the control animals developed fulminant disease and succumbed to the MARV challenge by day 12. MARV disease in the controls was indicated by: high titres of MARV (10(3)-10(5) plaque-forming units per mL); development of leucocytosis with concurrent neutrophilia at end-stage disease; and possible damage to the liver, kidney, and pancreas. Postexposure protection against MARV in non-human primates provides a paradigm for the treatment of MARV haemorrhagic fever. Indeed, these data suggest that rVSV-based filoviral vaccines might not only have potential as preventive vaccines, but also could be equally useful for postexposure treatment of filoviral infections.