on July 28, 2011
The finding, published on July 28 in the prestigious journal Science could lead to the production of a universal vaccine that could protect against all seasonal flu viruses as well as new pandemics. The discovery is the result of a collaboration between the IRB (Prof. Antonio Lanzavecchia, director and professor of immunology IRB human at the Swiss Federal Institute for Technology Zurich, ETH), the Humabs BioMed SA in Bellinzona (Dr. David Corti) and the National Institute for Medical Research (Prof. John Skehel) in London.
It’s called “FI6” and is the first antibody that can block all influenza A viruses: it could be used for prophylaxis and treatment of infections caused by influenza virus A.
The Science article describes how the IRB researchers have managed, using a new method for culturing the human plasma cells, to select those capable of producing an antibody that recognizes all the 16 subtypes of hemagglutinin of the influenza virus A.
The seasonal and pandemic influenza A viruses pose a serious threat to human health. Antibodies are immune molecules that play a key role in protecting against infection, but their effectiveness is limited by the extreme heterogeneity and variability of influenza viruses. The target of antibodies that block the infection is the hemagglutinin, a viral protein that mediates fusion between the virus and the infected cells. The hemagglutinin is evolving constantly evading the antibody response that is directed mainly towards the outer part, also called “head” of the hemagglutinin. So far 16 different hemagglutinin subtypes divided into two main groups: group 1 and group 2 are known. Usually the antibodies neutralize only certain viruses within a subtype, therefore new vaccines must be produced each year to protect against the new circulating viruses.
The IRB researchers have demonstrated that the FI6 antibody can bind all the 16 subtypes of hemagglutinin and neutralize seasonal viruses from group 1 and group 2, pandemic viruses including the “Spanish” virus from 1918, and even the bird and swine influenza viruses. The study also revealed that multiple mechanisms contribute to the protective effect of the antibody administered in vivo to prevent or treat infection. In particular, the antibody is able not only to block the viral entry into cells and its spread in the body but also to recruit the killer cells from the immune system to eliminate the infected cells.
X-ray crystallography studies have identified the binding site of the FI6 antibody which localizes in a conserved region in the “stem” of the hemagglutinin. This region can be considered as the “Achilles’ heel” of the virus and its structure can be exploited in order to design universal vaccines capable of inducing antibodies with the same specificity as FI6 and therefore able to neutralize all influenza viruses.
This project was funded by the European Research Council, the Swiss National Science Foundation, the Helmut Horten Foundation, the Human Frontier Science Program and the Wellcome Trust.
