Investigative therapeutic candidate made with four antibodies bound together shows the promise of influenza A and B … As a…
Investigative therapeutic candidate made with four antibodies bound together shows the promise of influenza A and B …
As a researcher in international collaboration, researchers at Scripps Research have discovered that tethering of four antibodies together can be one effective strategy to neutralize all types of influenza viruses that are known to infect humans.
Research suggests that this strategy can lead to the effectiveness of influenza-enhancing tools with strength and strength during the flu season, although the virus is rapidly mutating.
“We do not have a vaccine that protects against all the two main types of influenza (A and B). The key to this study is the construction of a multidomain antibody that is cross-neutralizing against influenza A and B,” says Ian Wilson, DPhil, Hansen Professor of Structural Biology at Scripps Research and Chairman of the Department of Integrated Structural and Database Biology.
Fusion of antibodies is not a new concept, but this is the first time that four antibodies have been tied together and tried against the flu.
The antibodies in This study came from llamas challenged with a vaccine containing three types of virus, as well as a key protein from two different influenza strains. Llamas are important in immunology research because they produce unique antibodies that are smaller and easier than those found in humans and fit into smaller and more recessed binding sites on the viral surface.
“In this case, lamb α antibodies are easily linked together to create multiple specific antibodies that bind to different sites on different targets, “says Dr. Wilson. “This multispecificity is the key to broad coverage of highly variable pathogens such as flu.”
The researchers linked two lama antibodies to influenza A and two to influenza B to create a “multidomain” antibody. With his researchers in Scripps Research, Ian Wilson and Professor Andrew Ward led X-ray and electron microscopy structural studies to show exactly where this multidomain antibody was binding on influenza proteins.
They found that the antibody could target several exposed sites for influenza A and B. This means that the antibody was cross-reactive and able to protect against all circulating strains of the virus affecting humans, as well as new subtypes that may mutate to cause pandemics.
“The question was then how to deliver these antibodies,” said Dr. Wilson.
For this, researchers turned to an approach traditionally used in gene therapy, not vaccine design. They used a viral vector capable of delivering a specially engineered gene to instruct cells to begin expressing a producing protein consisting of fragments from all four lamella antibodies.
The viral vector, called adenovirus-associated virus, was then administered in the nostrils of mice through a nasal spray. The goal was to make them produce these protective antibodies in their upper respiratory tract, the most exposed to the flu.
Collaborators at the University of Pennsylvania, led by Dr. James Wilson and Dr. Maria Limberis, found that this approach could provide protection against multiple influenza strains ̵
1; and it worked quickly within a few days in most mice.
Although the study suggests that a multidomain antibody target can contain potential as a strategy for the prevention of influenza A and B, this research is preclinical and further studies are required to determine if such a drug can be successfully developed.
The study has been published this week in Science.