‘Using two groups of monoclonal antibodies (mAbs) that show different activity profiles and different site-specificity could be useful in the inhibition of multiple steps of Ebola virus infection. This could provide a reliable therapeutic approach.’
The Ebola virus epidemic that happened in West Africa from 2013 to 2016 resulted in 28,000 cases and more than 11,000 people dying - hence, there is an urgent need for treatments against this virus and the family the virus belongs to, which are the highly pathogenic filoviruses.
There is still no licensed therapeutic available against the filovirus disease, in spite of intense international collaborative efforts. In order to develop effective antibody-based therapies for filovirus infections, we require a better understanding of the mechanism underlying their protective effect. So far, the impact on multiple steps of filovirus infection is not clear, although we know that the human immune system can produce strong antibody responses against the virus.
Study - Unravelling the mechanism of antibody defense
Ilinykh and his colleagues obtained a diverse panel of monoclonal antibodies (mAbs)
from several survivors of natural Ebola virus to understand their antiviral effects.
Glycans are major components of the viral surfaces, and hence glycans and their receptors play very significant roles when human hosts and viruses interact. When glycans are attached to proteins, they are known as glycoproteins which are also involved in infection and immunity.
The team of scientists discovered that monoclonal antibodies that targeted only the glycan caps inhibited viral attachment to the cell surface, cell-to-cell transmission and virion (an infected virus particle) budding. On the other hand, stem-specific antibodies that targeted the stem region of the viral glycoprotein triggered the activation of natural killer cells and the destruction of infected cells by monocytes and neutrophils (natural killer cells, monocytes, and neutrophils are all types of white blood cells).
Hence, each kind of antibody interfered with and targeted different steps of filovirus infection.
Taken together, the findings suggest that two groups of mAbs exerted cooperative effects by blocking distinct steps of filovirus infection. The authors suggest that antibody cocktails that combine complementary antiviral effects should be tested in future studies.
Alexander Bukreyev adds, "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."
Ebola Virus Disease Ebola virus disease or EVD
is an acute, severe illness in humans. It is transmitted to humans from wild animals and spreads through human-to-human transmission. If untreated, the disease is often fatal.
There have been 2 outbreak periods of the Ebola virus so far - two simultaneous ones in 1976 in Central Africa, and between 2013-2016 in West Africa. The latter was a larger, more complex and widespread outbreak that occurred in urban as well as rural settings.
Fruits bats are assumed to be natural Ebola virus hosts. The virus gets into human population through close contact with the blood, secretions, organs or other bodily fluids of infected animals such as chimpanzees, gorillas, fruit bats, and a few other animals found ill or dead in the rainforest.
Among humans, the virus spreads via direct contact with the blood, secretions, organs or other bodily fluids of infected people or inanimate objects like bedding that are contaminated with the fluids; it enters the body through broken skin, cuts or wounds.
The infection remains as long as the virus is in the blood.
Outbreaks have mostly been controlled by community efforts like interventions, infection preventions and control practices, a good laboratory service, safe and dignified burials and social mobilization.
Supportive measures like rehydration with oral or intravenous fluids and treatment of specific symptoms have been shown to improve survival. There is as yet no licensed treatment proven for EVD - however, there is a range of blood, immune therapies and drug therapies under development.
There is currently an experimental Ebola vaccine called rVSV-ZEBOV
that has proved highly protective against the deadly virus in a major trial in Guinea. Reference :
- Philipp A. Ilinykh, Rodrigo I. Santos, Bronwyn M. Gunn, Natalia A. Kuzmina, Xiaoli Shen, Kai Huang, Pavlo Gilchuk, Andrew I. Flyak, Patrick Younan, Galit Alter, James E. Crowe, Alexander Bukreyev., "Asymmetric antiviral effects of ebolavirus antibodies targeting glycoprotein stem and glycan cap". PLOS Pathogens, (2018); 14 (8): e1007204 DOI: 10.1371/journal.ppat.1007204