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Single-Domain Antibodies Arrest RSV Fusion Protein, Preventing Infection

FEB 17, 2017 | LAURIE SALOMAN, MS
Respiratory syncytial virus, also known as RSV, is the top cause of lower-respiratory-tract infections in children under age five worldwide. Roughly 33.8 million children in that age group are infected yearly, with more than 3 million requiring hospitalization because of the resulting bronchiolitis or pneumonia. The virus is also a big problem for elderly individuals. Because contracting RSV provides very little natural immunity against the disease, it is possible to become infected again and again throughout the lifespan.
 
Even though RSV has a huge impact on the health of both young and old people, the medical community has not yet come up with a licensed RSV vaccine. While antiviral drugs may be offered in rare instances, in most cases treatment consists of supportive care to ensure that the patient is as comfortable as possible and not in danger of dehydration. However, a team consisting of researchers from Ghent University and the Flanders Institute for Biotechnology (VIB) in Belgium, the National Institutes of Health, and the Geisel School of Medicine at Dartmouth University in Hanover, New Hampshire, recently tested a new antiviral therapy in mice that they hope will become available for use in humans.
 
The scientists isolated single-domain antibodies, also called Nanobodies, from dromedaries, camels, alpacas, and llamas. According to the study, these Nanobodies need to bind to only one part of the RSV fusion protein responsible for infection in order to prevent the RSV from entering the lungs. Bert Schepens, PhD, a biotechnologist at Ghent University and VIB and a corresponding author of the study elaborated, “Because [the Nanobody] is a very small size, it’s also very stable,” Dr. Schepens explained that this stability allows the antibody to withstand physical forces that might normally destroy more conventional antibodies: “This is the big advantage of Nanobodies—they can be nebulized and delivered directly to the lungs.” Conventional antibodies, with their greater instability, must be injected into the body; less than 1% of them will end up in the lungs.
 
According to Dr. Schepens, babies with RSV infections are more likely to benefit from Nanobodies than older individuals. This is because babies with RSV exhibit particularly high levels of the virus in their lungs. Elderly individuals with RSV, by contrast, have much less viral replication and are more likely to have comorbidities such as heart disease and COPD that contribute to their illness—conditions against which Nanobodies are unlikely to be effective. The team’s goal is to offer the therapy to babies with RSV infection in order to both shorten the duration of the infection and prevent a fatal outcome.
 
“Typically, babies end up in the hospital one or two days before the peak of the infection,” said Dr. Schepens. “It would be...ideal to start with the Nanobody therapy before the baby enters the hospital.” Although 1% to 2% of babies in the United States are admitted to the hospital for RSV every year, RSV-related deaths in babies are relatively rare in the United States. Developing countries, by contrast, have a high RSV mortality rate—anywhere from 66,000 to 199,000 babies killed per year.
 
The team hopes to pair with partners in order to do further testing on animals and eventually make Nanobody therapy available to humans.
 
Laurie Saloman, MS, is a health writer with more than 20 years of experience working for both consumer and physician-focused publications. She is a graduate of Brandeis University and the Medill School of Journalism at Northwestern University. She lives in New Jersey with her family.
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