Monoclonal Antibody Combo Reduces Marburg Disease Risk

A recent study conducted at the Galveston National Laboratory at The University of Texas Medical Branch at Galveston (UTMB) has shown a significant benefit to combining monoclonal antibodies and the antiviral remdesivir (Veklury) against advanced Marburg virus.

Marburg hemorrhagic fever is a severe and highly fatal disease caused by a virus from the same family that causes Ebola, says the World Health Organization (WHO).

In this study published in the journal Nature on March 25, 2021, using a rhesus model, treatment with monoclonal antibodies began six days post-infection, a critical point in disease progression. 

The combination therapy with the antiviral remdesivir showed an 80% protection rate, indicating promise for the treatment of advanced Marburg infections.

"Marburg is a highly virulent disease in the same family as the virus that causes Ebola. In Africa, patients often arrive at a physician very ill. It was important to test whether a combination of therapies would work better with really sick people,” stated Tom Geisbert, a professor in the Department of Microbiology & Immunology at UTMB and the principal investigator for the study, in a press release issued on March 25, 2021.

"Our data suggests that this particular combination allowed for recovery when given at a very late stage of the disease."

The Marburg virus is transmitted to people from fruit bats and spreads among humans through human-to-human transmission. The average Marburg case fatality rates have varied from 24% to 88% in past outbreaks depending on virus strain and case management, says the WHO.

Two large outbreaks that occurred simultaneously in Marburg and Frankfurt in Germany, and in Belgrade, Serbia, in 1967, led to the initial recognition of the disease. 

The outbreak was associated with laboratory work using African green monkeys imported from Uganda. Subsequently, outbreaks and sporadic cases have been reported in Angola, the Democratic Republic of the Congo, Kenya, South Africa, and Uganda. 

In 2008, two independent cases were reported in travelers who had visited a cave inhabited by Rousettus bat colonies in Uganda.

No local Marburg cases have been confirmed in the USA.

Dr. Zachary A. Bornholdt, Senior Director of Antibody Discovery and Research for Mapp Biopharmaceutical and a co-author on the study, said, "Often small molecules and antibodies are positioned to compete with each other for a single therapeutic indication.” 

“Here we see the benefit of pursuing both treatment strategies in tandem and ultimately finding synergy upon combining both approaches."

Geisbert, Bornholdt, and a large team at UTMB, Mapp Biopharmaceuticals, and Gilead Sciences have been developing monoclonal antibody (mAbs) therapies to treat hazardous viruses like Marburg and Ebola for several years. 

The mAbs treatments have proven to be highly effective in laboratory studies and emergency use, mainly when delivered early in the disease course.

Gilead's Veklury has demonstrated in vitro and in vivo activity in animal models against the viral pathogens MERS and SARS-1, which are also beta coronaviruses, and are structurally similar to SARS-CoV-2, that causes COVID-19 in humans.

On October 22, 2020, Gilead announced that the U.S. Food and Drug Administration had approved Veklury (remdesivir) for use in adult and pediatric patients 12 years of age and older and weighing at least 40 kilograms (about 88 pounds) for the treatment of COVID-19 requiring hospitalization.

This study was supported by the Department of Health and Human Services, National Institutes of Health grant U19AI142785 and UC7AI094660 for BSL-4 operations support of the Galveston National Laboratory. The researchers disclosed no industry conflicts of interest.

The University of Texas Medical Branch is Texas' first academic health center opened its doors in 1891. Today UTMB has four campuses, four health sciences schools, four institutes for advanced study, a research enterprise that includes one of only two national laboratories dedicated to the safe study of infectious threats to human health, a Level 1 Trauma Center, and a health system offering a full range of primary and specialized medical services throughout the Texas Gulf Coast region. 

UTMB is an institution in the University of Texas System and a member of the Texas Medical Center.

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