Attached antibodies can prevent infections with the flu virus

As co-leaders of an international collaboration, scientists at Scripps Research have discovered that attachment of four antibodies can be an effective strategy for neutralizing all types of influenza viruses known to infect humans.

Research suggests that this strategy could lead to influenza prevention tools that have the strength and power to last through the influenza season, even if the virus mutates rapidly.

"We do not have a vaccine yet that protects against the two main types of influenza (A and B). The key to this study is the development of a multidomain antibody that neutralizes the influenza A and B viruses. "Says Ian Wilson, DPhil, Professor of Structural Biology at Hansen's Scripps and Director of the Department of Structural Biology and Integrative computing. .

Tying together antibodies is not a new concept, but it is the first time that four antibodies are tied together and tried against the flu.

The antibodies in this study come from llamas that have been tested with a vaccine containing three types of viruses, as well as a key protein from two different strains of the flu. Llamas play an important role in immunology research because they produce unique antibodies, smaller and simpler than those found in humans, which fit into smaller binding sites and more indented on the viral surface. .

"In this case, llama antibodies could be easily bound together to create multi-specific antibodies binding to different sites on different targets," says Dr. Wilson. "This multi-specificity is the key to having a wide coverage of highly variable pathogens like the flu."

Scientists have combined two anti-influenza A llamain antibodies and two anti-influenza B antibodies to create a "multidomain" antibody. Together with colleagues at Scripps Research, Ian Wilson and Professor Andrew Ward led the structural studies in fluoroscopy and electron microscopy to show exactly where this multidomain antibody binds to influenza proteins.

They discovered that the antibody could target several vulnerable sites of influenza A and B viruses. This means that the antibody is cross-reactive and may be able to protect against all strains of the virus. circulating that affect humans, as well as against new subtypes likely to mutate. cause pandemics.

"The question then was how you could deliver these antibodies," says Dr. Wilson.

For this, scientists have turned to an approach traditionally used in gene therapy, not in vaccine design. They used a viral vector capable of transmitting a gene specifically designed for cells to begin expressing a producer protein composed of fragments of the four anti-llama antibodies.

The viral vector, called the adenovirus-associated virus, was then administered into the nostrils of mice via a nasal spray. The goal was to get them to produce these protective antibodies in the upper respiratory tract, the tissues most vulnerable to the flu.

Staff at the University of Pennsylvania, led by Dr. James Wilson and Dr. Maria Limberis, discovered that this approach could provide protection against several strains of influenza and worked quickly in a few days in most mice.

Although the study suggests that a multi-domain antibody approach could be a potential strategy for the prevention of influenza A and B viruses, this research is preclinical and further studies are needed to determine if such a drug can be developed with success.

The study was published this week in Science.