Postexposure Marburg vaccination protects monkeys

May 2, 2006 (CIDRAP News) An experimental vaccine protected monkeys from the deadly Marburg hemorrhagic fever virus even though they weren't vaccinated until after exposure, according to a report published in the April 29 issue of The Lancet.

The finding suggests that the vaccine could be effective for postexposure protection of laboratory or healthcare workers accidentally exposed to the Marburg virus, says the report by a team of US and Canadian researchers.

There is no licensed vaccine and no specific treatment for Marburg fever, which resembles Ebola hemorrhagic fever and is fatal in most cases. A Marburg epidemic in Angola in 2004 and 2005 killed 227 of 252 people infected, according to Angolan government figures.

The Marburg vaccine is based on a modified version of the vesicular stomatitis virus (VSV), which causes mouth inflammation in livestock. Researchers made the vaccine by inserting a surface glycoprotein gene from the Marburg virus into a live but weakened recombinant form of VSV (rVSV). In a previous study, the vaccine protected four monkeys when they were exposed to the virus 4 weeks after vaccination.

In the new study, eight rhesus macaques were injected with 1,000 plaque-forming units (pfu) of Marburg virus. About 20 to 30 minutes later, five of the monkeys were injected with the experimental vaccine, and the other three were injected with nonspecific rVSV formulations for control purposes. The time interval was assumed to be about how long it would take to vaccinate someone after an accidental needlestick exposure. The experiment was conducted in a biosafety level 4 lab at the US Army Medical Research Institute of Infectious Diseases (USAMRIID) in Maryland.

Although three of the five immunized monkeys had a fever by the sixth day after exposure, all five of them survived, the report says. In contrast, the three control monkeys all died by the 12th day, after showing signs of Marburg fever. The controls all had high levels of Marburg virus in their blood by day 6. Polymerase chain reaction testing showed transient viremia in four of the five treated monkeys on day 3, but plaque assays revealed no Marburg virus in their plasma at any point.

In assessing immune responses after 10 days, the researchers found low to moderate amounts of immunoglobulin M (IgM) against Marburg in four of the five treated monkeys and moderate amounts of IgG in all five. However, no cellular immune response was detected.

The authors write that the Marburg virus dose they used represents a worst case for a needlestick accident. Because many human exposures probably involve much smaller amounts of virus, the "window" for postexposure immunization is probably longer than 20 to 30 minutes, they suggest. Future animal studies, the report says, should focus on how long after exposure the vaccine can be used successfully and whether the vaccine used in this study, based on the Musoke strain of Marburg, will work against other strains.

The vaccine's protective mechanism in rhesus macaques remains to be determined, the article says. However, the same is true of postexposure protection conferred by rabies and smallpox vaccines in humans.

The authors conclude, "These results evidently have important clinical implications, and offer a new treatment approach for [Marburg] haemorrhagic fever and perhaps for other viral haemorrhagic fevers."

The research team included Kathleen M. Duddario-DiCaprio of USAMRIID as first author, along with other scientists from USAMRIID, the Uniformed Services Universtiy of the Health Sciences in Bethesda, Md.; Canada's National Microbiology Laboratory in Winnipeg, Man.; the University of Manitoba, Winnipeg; and the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

Daddario-DiCaprio KM, Geisbert TW, Stroher U, et al. Postexposure protection against Marburg haemorrhagic fever with recombinant vesicular stomatitis virus vectors in non-human primates: an efficacy assessement. Lancet 2006 Apr 29;367:1399-404 [Abstract]