Postexposure protection against Marburg haemorrhagic fever with recombinant vesicular stomatitis virus vectors in non-human primates: an efficacy assessment.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Daddario-DiCaprio
Kathleen M
KM
Virology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.
Geisbert
Thomas W
TW
Ströher
Ute
U
Geisbert
Joan B
JB
Grolla
Allen
A
Fritz
Elizabeth A
EA
Fernando
Lisa
L
Kagan
Elliott
E
Jahrling
Peter B
PB
Hensley
Lisa E
LE
Jones
Steven M
SM
Feldmann
Heinz
H
D000818:Animals; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008253:Macaca mulatta; D008379:Marburg Virus Disease / Q000276:immunology / Q000517:prevention & control*; D029024:Marburgvirus / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*; D014765:Viral Vaccines
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014765:Viral Vaccines