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Human antibody may help in discovery of Ebola virus therapy

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[FILE] A health care worker prepares a colleague’s Ebola virus protective gear at an Ebola virus clinic operated by the International Medical Corps in Makeni, Sierra Leone. Photo: AP


As the death toll of Ebola Virus (EBOV) increased to 55 in the Democratic Republic of Congo, researchers have intensified efforts to discover treatment against the virus and its related highly pathogenic filoviruses.

Ebola virus is a member of the filovirus family of enveloped, negative-strand RNA viruses and a zoonotic pathogen noted for its ability to cause severe disease in people, often fatal, and viral hemorrhagic fevers.The quest for vaccine grew increasingly urgent during the Ebola virus epidemic that killed over 11,300 people in the West African states of Guinea, Liberia, Nigeria and Sierra Leone from 2013 to 2016.

The infectious virus has long been considered incurable, even with the intense international collaborative efforts, there is still no licensed therapeutic available against filovirus disease. Though, swift isolation and rapid treatment of symptoms such as vomiting, diarrhoea and dehydration has helped some patients to survive, research has shown that further progress in the development of effective antibody-based therapies for filovirus infections, which requires a better understanding of the mechanism underlying their protective effect is a right step towards developing treatment.

Also, while the human immune system can produce strong antibody responses against filoviruses, the effects on multiple steps of filovirus infection have not been clear.According to a recent study published on August 2018, in the open-access journal PLOS Pathogens by Philipp Ilinykh and other colleagues from the University of Texas Medical Branch, Vanderbilt University, and Ragon Institut, there are two types of human antibodies that target different parts of the Ebola virus, which synergize their antiviral effects by inhibiting different steps of infection.

These new insights into how the human immune system protects against Ebola infections could lead to the development of effective antibody-based therapies, the study indicates. Ilinykh and colleagues in truing to address this gap in knowledge, evaluated the mechanisms underlying the antiviral effects of a diverse panel of monoclonal antibodies obtained from several survivors of natural Ebola virus infections.

These monoclonal antibodies that targeted either the glycan cap or stem region of the viral glycoprotein interfered with and targeted different steps of filovirus infection. The study showed that the glycan cap-specific antibodies inhibited viral attachment to the cell surface, cell-to-cell transmission and virion budding, in which by contrast, the stem-specific antibodies triggered the activation of natural killer cells and the destruction of infected cells by monocytes and neutrophils.

The findings suggested that the different types of antibodies exert cooperative effects by blocking distinct steps of filovirus infection. And according to the authors, antibody cocktails that combine complementary antiviral effects should be tested in future studies.One of the authors, Bukreyev added: “The current approach for treatment of filovirus infections with antibody cocktails tested in animal models utilizes the principle of targeting of non-overlapping epitopes. Our study suggests that possible synergistic effects of antibodies which block various steps of viral replication should be also considered.”


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