Big scoop: researchers from around the world have successfully immunized mice against both influenza A and B virus strains. For this they have grafted through a nasal spray a product based on llama antibodies, according to work published in science. Work that generates hope, while the flu has caused 13,000 deaths during the 2017-2018 epidemic.
Antibodies are large, Y-shaped molecules produced by our immune system in response to an attack by an external agent. The ends are made to specifically recognize the current threat. With regard to influenza, our antibodies recognize a protein on the surface of the virus called hemagglutinin. However, if this protein is present on all types of influenza viruses, it will vary depending on the influenza viruses found in the 60 attacking individuals, classified as type A or B. Therefore, current vaccines should focus on a specific strain to have the best chance to immunize against those who will gain the upper hand in the current year. It is this element of uncertainty that the effectiveness of the vaccine varies between 20 and 60%. "We do not have a vaccine that protects against the two main types of flu (A and B) " said Ian Wilson, a structural biologist at the Scripps Research Institute in San Diego, California, who helped understand the link between the synthesized antibodies and the virus.
A multi-antibody inspired by llama antibodies
To target multiple strains at the same time, it would be necessary … An antibody with different heads. Problem, our antibodies – and those of many other animals – are too big to be agglomerated into an effective product. But according to a study published in May 2018 in sciencesome species even have significantly smaller and lighter antibodies than other animals. Among them: camels, llamas & even sharks! By making them a little shorter, llama antibodies therefore produce mini-antibodies, called nanobodies, that are able to bind to smaller parts of the viral haemagglutinin.
For the research, the scientists, some of whom work for the Janssen laboratory, the owner of some of the molecules involved, have looked at llama's. They gave them a vaccine that contained three types of viruses, as well as a key protein from two different types of flu. They then combined two anti-influenza A lamain antibodies and two anti-influenza B antibodies to create a "multi-domain" antibody capable of targeting various vulnerable sites of the influenza A and B viruses. researchers were able to accurately visualize where this antibody binds to influenza proteins. This new antibody can potentially protect against all strains of the circulating virus that affects humans, and against new subtypes that can mutate and cause pandemics.
The mice were immunized against the main strains of the influenza virus
But how should this multi-antibody be administered? Usually the antibodies are produced spontaneously by the attacked organism. But here it was necessary to have him produce modified antibodies on a large scale. To achieve this, scientists have applied a well-known approach in the field of gene therapy. They first developed a gene that codes for their antibody and introduced it into a viral vector (modified virus). This virus could thus be introduced into the cells and be able to integrate the gene. The latter will then be "read" by the cell and converted into protein such as the rest of its genetic material to form the multi-antibody.
To test this method, mice received the viral vector by injection or in the nostrils, a highly vascularized area, via a nasal spray. The goal was to have them produce these protective antibodies in the upper respiratory tract, the tissues most susceptible to influenza. The results are "impressive scale and strengthAccording to the publication, the treated mice had indeed significantly higher survival rates than untreated rodents when inoculated with different strains of influenza (influenza virus), mainly by nasal spray.
Not necessarily transposable to humans
However, these results are only preliminary and do not necessarily predict much prosperity for success in humans. Our immune system was able to identify lama-derived nanobodies as intruders and antibodies against them, warns immunologist James Crowe, flu specialist and vaccine developer at Vanderbilt University in Nashville, in a statement. . Moreover, according to him, viral vector therapy is likely to be subject to increased regulatory oversight, because it is a DNA modification. Until now used for life-threatening diseases, viral vectors can be a problem in the prevention of influenza. "The bar for administering a viral vector to a healthy person will be very high", he warns.