Ebola virus
- Article
- 2021-01-30
Ebola virus disease, first recognized in the Democratic Republic of Congo in 1976, is a serious and often fatal disease in humans and non-human primates. Four of the six known virus species of the Ebola virus genus are known to infect humans and cause Ebola virus disease. They are spread by direct contact with a patient's body fluids and can cause fever, headache, muscle pain, weakness, fatigue, diarrhea, vomiting, abdominal pain and bleeding (severe bleeding).
The Ebola virus is part of the family Filoviridae , which also includes the Marburg virus. Marburg virus disease was first recognized in 1967 and is characterized by the same symptoms and pathways of transmission as Ebola virus disease. There are two known types of Marburg virus that can cause disease in humans and non-human primates.
Therapy
The NIAID conducts and funds research into various experimental Ebola treatments, with the aim of alleviating suffering and stopping the spread of disease.
In November 2018, NIAID and the Democratic Republic of the Congolese National Institute for Biomedical Research (INRB) began a phase 2/3 clinical trial testing multiple experimental Ebola therapies. The trial, known as PALM (short for "Pamoja Tulinde Maisha", a Swahili phrase roughly translated to "save lives together") was conducted by a research consortium overseen by the World Health Organization, including non-governmental organizations and the Ministry of Public health of the DRC. It was designed to compare mortality between patients who received any of the three study drugs (mAb114, REGN-EB3 and remdesivir), with a control group of patients who received the experimental cocktail treatment with monoclonal antibodies ZMapp. Preliminary results announced in August 2019 indicated that patients who received REGN-EB3 and mAb114 had a greater survival rate compared to patients who received ZMapp or remdesivir. The results prompted an independent data and safety monitoring board to recommend that the study be discontinued and that all prospective patients be randomized to receive REGN-EB3 or mAb114 in an extension phase of the study. See below for more information on research treatments investigated by the NIAID.
mAb114
mAb114 is a monoclonal antibody isolated from a survivor of the 1995 Ebola epidemic in the Democratic Republic of Congo. It was discovered by researchers at the NIAID's Vaccine Research Center (VRC), in collaboration with the INRB in DRC. VRC initially developed and produced the mAb114 antibody product, which is now licensed to Ridgeback Biotherapeutics for advanced development.
mAb114 binds to an extremely conserved region on the Ebola virus (specifically the Zaire virus species) to block its interactions with a receptor on human cells. This prevents the virus from entering and infecting cells. A single dose of mAb114 completely protects non-human primates five days after fatal Ebola virus infection, and the results of a phase 1 clinical study of mAb114 indicated that the study treatment is safe.
ZMapp
NIAID supported the early development and preclinical testing of ZMapp, a "cocktail" of three different monoclonal antibodies. The antibodies bind to three different regions of the Ebola virus glycoprotein to inhibit viral replication.
During the first experiments, the antibodies were produced in tobacco plants that were specially developed to produce large amounts of the proteins. They can also be produced in a cell line derived from hamster ovaries (known as CHO cells).
ZMapp was administered with emergency use permission to Ebola-infected patients during the 2014-2016 outbreakml; nts. NIAID and the Liberian Ministry of Health, under the PREVAIL- partnership, started a Phase 2 clinical trial which examined the safety and efficacy of zmapp. The results indicate that the antibody cocktail was well tolerated and showed promise, but there was insufficient data to definitively establish whether it is a better treatment for Ebola virus disease than supportive care alone.
Shortly after the DRC announced an outbreak of the Ebola virus disease in August 2018, ZMapp was made available to Ebola patients under an expanded access or compassionate use framework. BARDA has supported the advanced development of ZMapp. However, ZMapp is no longer administered to patients with Ebola virus disease in the DRC after preliminary results from the PALM study indicated that mAb114 and REGN-EB3 are superior.
The NIAID Centers of Excellence for Translational Research (CETR) program supports research on immunotherapeutics against viral haemorrhagic fever . Researchers funded through the CETR program identified the structure of ZMapp and how it binds to Ebola virus, and are now using this knowledge to test the next generation of antibodies for better binding and efficacy.
GS-5734 (brake desivir)
The experimental antiviral agent GS-5734, also known as remdesivir, is being developed by Gilead as a treatment for Ebola virus disease. NIAID is studying its ability to remove Ebola virus RNA from the sperm of Ebola survivors in a study in Liberia known as PREVAIL 4 . Remdesivir will no longer be administered to patients with Ebola virus disease in DRC after preliminary results of the PALM trial were announced. However, the antiviral agent is being considered for combination therapy, which should first be investigated in preclinical studies.
BCX4430
BCX4430 (also known as galidesivir), developed by BioCryst Pharmaceuticals with the support of NIAID, is an experimental drug with a small molecule and a broad spectrum of antiviral activity, including against Ebola. BCX4430 has protected animals from infection with Ebola and Marburg viruses, and clinical study of BCX4430 is ongoing
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