Monday July 16, 2018

‘Trojan Horse’ Antibody Strategy Shows Promise Against Ebola Virus

Monoclonal antibodies, which bind to and neutralize specific pathogens and toxins, have emerged as the most promising treatments for Ebola

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FILE - A health worker, center, takes the temperature of people to see if they might be infected by the Ebola virus inside the Ignace Deen government hospital in Conakry, Guinea, March 18, 2016. VOA
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Scientists have found a hidden weak spot shared by all five known types of the deadly Ebola virus and successfully targeted it with two antibodies that blocked its ability to invade human cells.

In early-stage laboratory experiments published in the journal Science, the researchers developed a “Trojan horse” strategy that allows engineered antibodies to hitch a ride on Ebola to where the virus is most vulnerable before hitting it.

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“The success in co-opting the virus itself to dispatch a lethal weapon … marks a turning point in the development of smart therapeutics against infectious diseases,” said M. Javad Aman, a scientist, and president at the U.S. biotech firm Integrated Bio Therapeutics who worked on the team.

Although years of testing lie ahead before any fully approved treatment might be developed for Ebola patients, Aman said similar strategies could also be devised against several other viral and bacterial pathogens.

No approved treatments

Ebola is an extremely deadly and contagious disease for which there are currently no regulator-approved vaccines or treatments. A vast outbreak of the Zaire strain of the virus, which causes haemorrhagic fever, killed more than 11,000 people and infected around 29,000 in West Africa in 2014-15.

Monoclonal antibodies, which bind to and neutralize specific pathogens and toxins, have emerged as the most promising treatments for Ebola. But a critical problem is that most antibody therapies — including the most promising experimental therapy, ZMapp — target only one specific Ebola virus.

Ebola Virus. Image Source: Wikimedia Commons.
Ebola Virus. Image Source: Wikimedia Commons

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In this work, the research team found a way around this by targeting a weak spot — in the so-called lysosome of the cell — to where antibodies could hitch a ride on Ebola and deliver a punch that blocked the virus’ exit and ability to replicate.

The strategy could eventually be developed for use in a range of other viruses, the scientists said, including cousins of Ebola such as Marburg, and other viral diseases such as dengue or Lassa.

“It’s impossible to predict where the next Ebola virus outbreak will occur or which virus will cause it,” said Jon Lai of the Albert Einstein College of Medicine in New York City, who co-led the work. “We hope that further testing in nonhuman primates will establish our antibodies as safe and effective for treating those exposed to any Ebola virus.”(VOA)

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Ultra-Secure Lab In Gabon To Handle World’s Most Dangerous Viruses

'Teams on alert'

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Dr. Mombo dons his white coat as he prepares to analyse samples at the Franceville International Centre of Medical Research (CIRMF) is seen on June 12, 2018 in Franceville.
Dr. Mombo dons his white coat as he prepares to analyse samples at the Franceville International Centre of Medical Research (CIRMF) is seen on June 12, 2018 in Franceville. VOA

At a research facility in Gabon, one isolated building stands behind an electrified fence, under round-the-clock scrutiny by video cameras. The locked-down P4 lab is built to handle the world’s most dangerous viruses, including Ebola.

“Only four people, three researchers and a technician, are authorized to go inside the P4,” said virologist Illich Mombo, who is in charge of the lab, one of only two in all of Africa that is authorized to handle deadly Ebola, Marburg and Crimean-Congo haemorrhagic fever viruses. The other is in Johannesburg.

The P4 was put up 800 metres (half a mile) distant from older buildings of the Franceville International Centre for Medical Research (CIRMF), in large grounds on the outskirts of Franceville, the chief city in the southeastern Haut-Ogooue province.

Filming the ultra-high-security lab or even taking photos is banned and the handful of people allowed inside have security badges. Backup power plants ensure an uninterruptable electricity supply. “Even the air that we breathe is filtered,” Mombo explains.

When he goes into the P4 lab to work on a sample of suspect virus such as Ebola — which has claimed 28 lives in the Democratic Republic of Congo (DRC) during an outbreak in the past six weeks — Mombo wears a head-to-foot biohazard suit.

The special clothing is destroyed as soon as he has finished. Draconian measures are in force to prevent any risk of contamination, with potentially disastrous effects.

Ebola Virus, Treatment
Ebola Virus, Treatment, Pixabay

‘Teams on alert’

Once a suspect virus has been “inactivated” — a technique that stops the sample from being contagious — it is carefully taken from the P4 unit to other CIRMF laboratories in the compound, where it is analysed.

Specialized teams will scrutinize it, looking to confirm its strain of Ebola and hunting for clues such as the virus’s ancestry and evolution, which are vital for tracking the spread of the disease.

CIRMF director Jean-Sylvain Koumba, a colonel in the Gabonese army and a military doctor, said lab teams had been “placed on alert” to handle Ebola samples sent on by the National Institute of Biomedical Resarch in the DRC capital Kinshasa.

The nature of the sample can be determined with rare precision, for the facility has state-of-the-art equipment matched in few other places worldwide.

“On average, it takes 24 to 48 hours between the time when a sample arrives and when we get the results,” Mombo said.

Founded in 1979 by Gabon’s late president Omar Bongo Ondimba to study national fertility rates, the CIRMF moved on to AIDS, malaria, cancer, viral diseases and the neglected tropical maladies that affect a billion people around the world, according to the WHO.

The center is financed by the Gabonese state, whose main wealth is derived from oil exports, and gets help from France.

In all, 150 people work for the CIRMF and live on the huge premises. Its reputation draws scientists, students and apprentices from Asia, Europe and the United States, as well as Africa.

“[The] CIRMF is uniquely suited to study infectious diseases of the Congolese tropical rain forest, the second world’s largest rain forest,” two French scientists, Eric Leroy and Jean-Paul Gonzalez, wrote in the specialist journal Viruses in 2012.

“[It] is dedicated to conduct medical research of the highest standard … with unrivaled infrastructure, multiple sites and multidisciplinary teams.”

African child suffering from Malaria and ebola
African child suffering from Malaria and ebola, Pixabay

Animal ‘reservoir’?

The facility also conducts investigations into how lethal tropical pathogens are able to leap the species barrier, said Gael Darren Maganga, who helps run the unit studying the emergence of viral diseases.

“A passive watch consists of taking a sample from a dead animal after a request, while the active watch is when we go out ourselves to do fieldwork and take samples,” he said.

A major center of interest is the bat, seen as a potential “reservoir” — a natural haven — for the Ebola virus, said Maganga. Staff regularly go out all over Gabon to take samples of saliva, fecal matter and blood.

The consumption of monkey flesh and other bush meat is common practice in central Africa.

Also read: Vaccination Campaign Against Ebola Virus Launched In Democratic Republic of Congo

“It’s still a hypothesis, but the transmission to human beings could be by direct contact, for instance by getting scratches [from a bat] in caves, or by handling apes which have been infected by bat saliva,” he said. (VOA)