Friday, February 27, 2015

Researchers identify antibodies to fight Marburg virus

Two new studies have demonstrated how human antibodies can neutralize the Marburg virus, a highly lethal virus related to Ebola.

Antibodies have been found to bind to the surface of the virus, which could lead to future antibody treatments and vaccines to target Marburg and other viruses in the family.

Marburg virus is up to 90% lethal. Just like the Ebola virus, it can cause hemorrhaging and organ failure. An outbreak of the virus in Angola in 2005 was responsible for the deaths of 329 people, and the worry is that an even bigger outbreak could occur in the future.

"The good news is, humans do make antibodies when they are
infected that can kill these viruses... which suggests that
vaccines should work," says Dr. James Crowe, lead author of one of the two studies published in Cell.

In Dr. Crowe's study, the antibodies that can neutralize
Marburg virus were isolated and characterized following
analysis of the blood of a woman diagnosed with the disease.

Following the identification of the antibodies, the team
confirmed their ability to kill the virus in the level 4 biosafety facility at the University of Texas Medical Branch (UTMB).

Co-author Dr. Andrew Ward says that the research leaves him
hopeful that a cross-reactive antibody treatment could be
designed in the future to fight Marburg and related viruses,
including the Sudan virus and Bundibugyo virus. "We need to
be prepared for future outbreaks," he states.

In the second study, researchers investigated precisely how the
antibodies bind to a vulnerable site on the Marburg virus.

To begin with, a team from The Scripps Research Institute
(TSRI) worked out how to grow crystals of the antibody that
were attached to the virus. By exposing these crystals to X-ray
diffraction, their shape was revealed in three dimensions.

The discovery of this shape enabled the team to demonstrate
how the antibodies attach to the virus, preventing it from
binding to receptors and transmitting its genetic material into human cells.

'A straightforward route to a therapeutic'

Due to the relationship between the Marburg and Ebola viruses, the researchers questioned whether the antibody would be able to neutralize Ebola in the same manner as this.

In order to investigate this possibility, the team used a
technique called small-angle X-ray scattering to examine the
carbohydrate-rich coating on the surface proteins of both viruses. The imaging process revealed that these regions had
different shapes that exposed different surfaces beneath.

Only in Marburg virus is the body able to create an antibody
the correct shape to affect an exposed region. Despite this,
senior author Prof. Erica Ollmann Saphire believes that the potential is there to one day create treatment for both viruses.

"These cross-reactive antibodies are a straightforward route to a therapeutic," she says. "You could use these antibodies directly against Marburg virus or - with a bit more engineering - use them to also target Ebola virus."

"Since we know where on the virus important antibodies bind,
that tells us what needs to be in the vaccine," Dr. Crowe adds.

Presently, researchers from Vanderbilt University in Nashville, TN, are working with a number of companies to produce large numbers of antibodies that could potentially be used to provide a measure of protection from infection.

Part of why the viruses are so dangerous is because of how
long it takes the body's immune system to effectively respond
to their attack - around 4-6 weeks. According to Dr. Crowe,
antibody injections shortly after exposure could be enough to prevent illness from fully developing.

The ultimate aim is to develop a vaccine that can provide long-
term protection. For now, Dr. Crowe hopes clinical safety and
dosage trials for the antibodies can be completed by the end of
the year.

At the end of last month, the World Health Organization (WHO) declared that the focus of efforts against Ebola is now
shifting from slowing transmission to ending the epidemic.