A genic nasal spray inspired by llama antibodies could prevent all types of influenza | Science

Four antibodies against the llama and a harmless virus: this strange recipe could form the basis of a nasal spray designed to counteract the infection of all strains of the flu. The spray, containing a virus designed to make a protein derived from the lama's antibodies, has passed its first test on animals, protecting mice from all known strains of flu that infect humans, a research team reported.

Although the strategy needs to be further tested before human trials can begin, researchers who have struggled to develop a "universal" vaccine against the highly mutable influenza virus say that It deserves serious attention. The nasal spray could be a boon to the elderly, who usually suffer from the flu and only benefit from a weak protection of existing vaccines. And unlike traditional influenza vaccines, tailored to each influenza season to match the circulating viruses, they could be stored for protection against an influenza pandemic. "It's a great story and shows the power of antibody engineering," says immunologist Antonio Lanzavecchia, a leading researcher on influenza vaccines at the Biomedicine Research Institute. from Bellinzona, Switzerland.

Antibody engineer Joost Kolkman of Janssen Infectious Diseases in Beerse, Belgium, and his colleagues thought that an unusual class of antibodies made by the lamas and their camel cousins ​​could serve as a source of information. 39, weapon against the flu. These antibodies are unusually small because they do not possess the "light" peptide chain that normally swells each arm of Y-shaped proteins. Researchers can further reduce the remaining "heavy" chains to create what is called nanobodies, able to penetrate the slots of viruses that their normal size counterparts can not touch.

To create nanowinds against influenza, the Janssen group injected llamas with a vaccine containing three different influenza viruses, as well as the viral surface protein, hemagglutinin, from two other strains of the influenza virus. They then harvested four antibodies, each of which neutralized many influenza strains. In the end, the team was able to design a gene expressing a protein composed of nanobodies derived from the four antibodies. "It's very easy to link domains to one molecule," says Kolkman. They spliced ​​the gene into a benign virus associated with adenovirus (AAV) used in gene therapy experiments.

Studies in the test tube showed that the four-in-one antibody prevented infection with 60 different influenza viruses from groups A and B infecting people. "It has been quite difficult to find an antibody that neutralizes A and B," says Ian Wilson, a structural biologist at the Scripps Research Institute in San Diego, California, who has helped to understand the link between nanobodies and the virus.

The mice that received the synthetic antibody – either by injecting the treated virus into their nose, or by infusing the protein directly into their circulation – had significantly higher survival rates than untreated rodents when they were injected with various strains of influenza. Wilson, who has published more than 50 articles on anti-influenza antibodies, says he has never seen one as rich and powerful. Since AAVs can persist for months, the strategy could offer extended production. "Hope this will last the entire flu season in humans," said Wilson.

Immunologist James Crowe, an influenza specialist and vaccine developer at Vanderbilt University in Nashville, warns that human immune systems may see the llama-derived proteins as foreign and develop antibodies against them. He also notes that, although AAV-based treatments are being tested for potentially life-threatening diseases, transmitting the virus as a prevention of influenza would be subject to increased surveillance from the regulatory authorities. "The bar to place AAV in a healthy individual is going to be very high," says Crowe.