AsianScientist (Oct. 9, 2017) – In a study published in the journal Cell, scientists in Singapore and Switzerland have generated a protein-based drug that can be used in the treatment of Zika virus infection.
The Zika virus belongs to the class of viruses called flaviviruses, which also includes the dengue and West Nile viruses. It is spread by mosquitoes and has reached large parts of the tropical and subtropical regions of the world, including parts of the United States.
While the symptoms of Zika virus infection can be absent or generally mild, the virus appears to invade the neural tissue of the fetus, leading to microcephaly and other neural defects in offspring in up to 13 percent of cases. The virus can also be spread by bodily fluids, including semen, making sexual transmission possible.
Although attempts have been made to reduce the spread of the virus by killing the mosquitoes with insecticides, there are currently no vaccines or treatments against Zika. Thus, there is an urgent need to develop therapies to treat this rapidly spreading disease.
“Zika virus infection has turned into a public health threat, particularly due to its association with severe congenital birth defects. The development of an effective vaccine to prevent Zika virus infection poses some risks, and it is important to develop new and alternative approaches,” said Dr. Davide Corti, Chief Scientific Officer of Humabs BioMed.
In this study, a group of researchers led by Associate Professor Lok Shee Mei of the Duke-National University of Singapore (NUS) Medical School developed a protein-based drug known as a bi-specific antibody, called FIT-1, that can neutralize the Zika virus. FIT-1 was designed in collaboration with Humabs BioMed, a Swiss biotechnology company, using its proprietary CellClone technology. It combines the specificities of both human antibodies ZKA190 and ZKA185.
ZKA190 is a potent Zika virus-neutralizing antibody shown to bind to all surface E proteins on the virus particle and distort the quaternary viral structure, while ZKA185 binds to a distinct sites on the virus and helps prevent viral escape. FIT-1 was shown to potently neutralize strains of the Zika virus isolated around the world, and the virus was unable to escape from it.
The interaction between virus and antibody was elucidated by a combination of experimental and computational techniques to understand how FIT-1 blocks the infection cycle. The work took advantage of a recently acquired nuclear magnetic resonance machine at the Institute for Research in Biomedicine (IRB) in Bellinzona, Switzerland.
Lok’s laboratory at Duke-NUS used electron microscopy imaging at extremely low temperatures to examine the binding effect of the ZKA190 antibody to the Zika virus under high magnification. ZKA190 was observed to break the surface structure of the Zika virus particle, thus explaining its high potency in clearing the virus.
The therapeutic potential of FIT-1 was evaluated in mice by administering three different doses (15, 5 and 1 milligrams per kilogram) at three different time points (one, two and three days post infection). While all doses provided protection against infection, the highest dose resulted in a 100 percent survival rate with no signs of morbidity, even when treatment was given three days post infection. No viral escape was detected at any of the dose levels at the measured time point of five days post infection.
“We have shown that Zika has a remarkable ability to change and evade the human immune response. We designed the FIT-1 bispecific antibody to overcome this problem,” said Dr. Luca Varani of IRB.
The researchers plan to conduct further experiments to determine FIT-1’s effectiveness in blocking fetal infection. They also hope to explore alternative delivery mechanisms for the antibody that could make it more cost effective and thus more accessible to the parts of the world most in need of cures for this disease.
“The FIT-1 antibody has potential to be developed as a therapeutic for the treatment and prevention of Zika virus infection in adults and pregnant women. Hopefully, clinical trials can be accelerated so that the FIT-1 antibody may be used in future outbreaks, as well as to tackle emergency cases of Zika infection in pregnant women,” Lok concluded.
The article can be found at: Wang et al. (2017) A Human Bi-specific Antibody against Zika Virus with High Therapeutic Potential.
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Source: Duke-NUS Medical School; Photo: Shutterstock.
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